EML4--ALK

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COSMIC CHIMERKB CHIMERPUB CHIMERSEQ CHITARS
FARE-CAFE TICDB TUMOR_FUSION_GDPFusionCancerConjoinG
1000Genome18CancersBodymap2HPANon_Tumor_Cells
Babiceanu_DatasetBanned_DatasetKnown_FusionsONGene DatabaseBushman Cancer Gene Database
Tumor Gene Set By UniprotOesophagus_DatasetGliomas_DatasetProstate_DatasetPancreases_Dataset
GTExKlijn_DatasetFimereli_Dataset Literature Cortex_Dataset
ChromothripsisDB

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EML4 ALK

COSMIC

The fusion gene pair EML4--ALK information is available in COSMIC database.

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EML4--ALK

ChimerKB

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The fusion gene pair EML4--ALK information is available in CHIMERKB (CHIMERDB 3.0) database.

Fusion_pair5'Gene Junction (Chr/Position/Strand)3'Gene Junction (Chr/Position/Strand)Breakpoint_TypeGenome_BuildDiseaseValidationPMIDGene TypeSource
EML4_ALK-/1751/ -/4080/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/929+220/ -/4080/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/2504/ -/4080/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/929/ -/4080/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/2318+654/ -/4080-172/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/929/ -/4080-18/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/2318/ -/4080/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/470/ -/4080-117/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/2029/ -/4080/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/2229/ -/4080/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/1751/ -/4080-69/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/1903/ -/4080/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/929/ -/3975/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/2229+2522/ -/4126/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/1751/ -/4080-90/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/1903/ -/4080-123/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/470/ -/4080/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/2504/ -/4080-18/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/929+805/ -/4080-115/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/1903/ -/4129/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/2504+182/ -/4080-67/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/1751+447/ -/4080-161/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/929+(7320)/ -/4080/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/2504+545/ -/4080-232/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/1751+(3600)/ -/4080-297/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/1751+1485/ -/4080-1254/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/1751+2575/ -/4080-203/ Exonic hg19 - - - Kinase; Oncogene; Cosmic_recurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 17625570 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 18242762 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 gastrointestinal cancers, breast cancers - 18414414 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 18594010 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 18593892 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 18166835 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 18320074 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 18927303 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung cancer - 19170230 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung cancer - 19383809 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 19667264 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 - - 19936840 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 19386350 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung cancer - 20813423 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 20624322 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 20855837 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 21168933 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 20926401 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 21102267 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung cancer - 21102268 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 21642865 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 mucinous adenocarcinoma - 21719143 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 21102269 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung cancer - 20979473 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 21036415 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 20659620 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 22080568 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 22129856 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 22124476 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 18083107 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 22140546 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 22317764 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 22323876 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 22277784 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 22327624 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 22569898 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 neuroblastoma - 21030459 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 22622260 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung cancer - 22425930 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 22706607 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 22707299 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 22736493 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 22768234 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 22100693 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 22964709 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 23060582 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 23098378 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 small cell lung cancer - 23154565 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 23181703 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 23198868 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 23277484 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung cancer - 23344087 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung cancer - 23372947 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 23415374 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 23408463 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 23341890 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 23439505 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 pulmonary adenocarcinoma - 23449277 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 23661334 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 23714228 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 23683537 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 23731739 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 small cell lung cancer - 23787064 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 papillary thyroid cancer - 23050789 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 23910397 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 22913857 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 23951022 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung cancer - 23609245 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 24123310 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 24133367 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 peripheral lung cancer - 24183104 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 24346091 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 24419120 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 24443522 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 adenosquamous lung carcinoma - 24481316 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 23675251 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 23919423 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 24736079 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 24700479 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung pleomorphic carcinoma - 24846683 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 24754584 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 24810493 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 24496003 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 pulmonary mucinous adenocarcinoma - 24913807 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 24992725 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 24982409 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 24469108 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 thyroid cancer - 24613930 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 25228534 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 25393796 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 thoracic neoplasm - 25393798 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung adenocarcinoma - 25496960 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 25736571 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 non small cell lung cancer - 24942894 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALK-/-/ -/-/ - hg19 lung cancer - 26464158 Kinase; Oncogene; Cosmic_nonrecurrent
EML4_ALKchr2/42492091/+ chr2/29446394/- Exonic hg19 - - - Kinase; Oncogene; GenBank
EML4_ALKchr2/42491871/+ chr2/29446394/- Exonic hg19 - - - Kinase; Oncogene; GenBank
EML4_ALKchr2/42522656/+ chr2/29446394/- Exonic hg19 - - - Kinase; Oncogene; GenBank
EML4_ALKchr2/42552694/+ chr2/29446394/- Exonic hg19 - - - Kinase; Oncogene; GenBank
EML4_ALKchr2/42526287/+ chr2/29446394/- Exonic hg19 - - - Kinase; Oncogene; GenBank
EML4_ALKchr2/42376164/ chr2/29269148/ Exonic hg18 - - - Kinase; Oncogene; ChimerDB2
EML4_ALKchr2/42406198/ chr2/29269148/ Exonic hg18 - - - Kinase; Oncogene; ChimerDB2
EML4_ALKchr2/42345595/ chr2/29269593/ Exonic hg18 - - - Kinase; Oncogene; ChimerDB2

ChimerPUB

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The fusion gene pair EML4--ALK information is available in CHIMERPUB (CHIMERDB 3.0) database.

Fusion_pairTranslocationPMIDDiseaseValidationGene TypeSentence_highlight
EML4_ALK- 27043019non small cell lung cancer;lung cancer FISH;PCR - NSCLC patients may carry a nonreciprocal translocation on human chromosome 2, in which synchronized double stranded breaks (DSB) within the echinoderm microtubule-associated protein-like 4 (EML4) gene and ALK lead to an inversion of genetic material that forms the non-natural gene fusion EML4-ALK encoding a constitutively active tyrosine kinase that is associated with 3 to 7% of all NSCLCs.
EML4_ALK- 25676400non small cell lung cancer;lung cancer FISH;PCR - The application of IHC, ARMS fluorescence quantitative PCR and FISH technology can make a rapid and accurate evaluation of EML4-ALK gene fusion.. /// "EML4-ALK gene fusion in 85 cases of paraffin embedded tumor tissue and adjacent lung tissue was detected with the application of immunohistochemistry (IHC), Scorpions amplification refractory mutation system (Scorpions ARMS) fluorescence quantitative PCR and fluorescence in situ hybridization (FISH) technology, and EGFR gene in 18, 19, 20 and 21 exon mutation status was detected with the application of ARMS method. " /// [Analysis of EML4-ALK gene fusion mutation in patients ?with non-small cell lung cancer]. /// " Non-small cell lung cancer (NSCLC) is the main type of lung cancer, and the related locus mutation detection research has become a hot direction of molecular targeted therapy, studying on gene mutation status of echinodem microtubule associated protein like 4-Anaplastic lymphoma kinase (EML4-ALK) and epidermal growth factor receptor (EGFR), detecting the sensitivity of EML4-ALK gene fusion and gene mutation of EGFR. " /// [Analysis of EML4-ALK gene fusion mutation in patients ?with non-small cell lung cancer].. /// "While FISH showed 23 cases with EML4-ALK fusion gene mutation, the detection rate was 20%, slightly lower than the ARMS detection results, suggesting that ARMS more sensitive. " /// "ARMS showed 27 cases with EML4-ALK fusion gene mutation, the mutation detection rate was 23.5%. "
EML4_ALK- 25609979non small cell lung cancer;lung cancer;adenocarc FISH - EML4-ALK gene fusions are present in lung adenocarcinomas from Indian patients, and the 3% incidence of EML4-ALK gene fusion in EGFR mutation-negative cases is similar to what has been observed in other Western and Asian populations. /// Clinical and epidemiological study of EGFR mutations and EML4-ALK fusion genes among Indian patients with adenocarcinoma of the lung. /// "Of the 336 EGFR-negative blocks, EML4-ALK fusion gene was present in 15 (4.5%) patients, whereas 321 (95.5%) tumors were EML4-ALK negative." /// The overall incidence of EML4-ALK fusion gene was 3% (15/500). /// Clinical and epidemiological study of EGFR mutations and EML4-ALK fusion genes among Indian patients with adenocarcinoma of the lung.. /// "Of the 336 EGFR-negative blocks, EML4-ALK fusion gene was present in 15 (4.5%) patients, whereas 321 (95.5%) tumors were EML4-ALK negative. " /// The mutual exclusivity of EML4-ALK and EGFR mutations suggests implementation of biomarker testing for tumors harboring ALK rearrangements in order to identify patients that can benefit from newer targeted therapies.. /// The objective of this study was to determine the prevalence of EGFR mutations and EML4-ALK fusions in Indian patients with NSCLC (adenocarcinoma) as well as evaluate their clinical characteristics. /// The objective of this study was to determine the prevalence of EGFR mutations and EML4-ALK fusions in Indian patients with NSCLC (adenocarcinoma) as well as evaluate their clinical characteristics.
EML4_ALK- 22742552non small cell lung cancer;adenocarcinoma FISH;PCR;RT-PCR - Echinoderm microtubule-associated proteinlike 4-anaplastic lymphoma kinase (EML4-ALK) gene fusions are detected in 3% to 13% of non-small cell lung carcinomas. /// "To compare reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH) methodologies for detection of EML4-ALK fusions." /// "To compare reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH) methodologies for detection of EML4-ALK fusions. " /// "EML4-ALK variant 3a/b was detectable by RT-PCR, FISH, and IHC in 4% (2 of 46) of specimens." /// "EML4-ALK variant 3a/b was detectable by RT-PCR, FISH, and IHC in 4% (2 of 46) of specimens. " /// No concordance existed among methodologies for the detection of EML4-ALK variant 1. /// One EML4-ALK variant 1 fusion was found to coexist with an EGFR exon 21 mutation. /// "Overall, the frequency of EML4-ALK variants 1 and 3a/b was 24% (11 of 46) in adenocarcinomas enriched for wild-type EGFR status. " /// The RT-PCR method was the most sensitive and least-subjective methodology for detection of EML4-ALK fusions.. /// Accurate testing for detection of EML4-ALK fusions is essential for appropriate therapy selection.
EML4_ALK- 20179225anaplastic large cell lymphoma;lung cancer;adenocarcinoma;lymphoma FISH - Approximately 5% of lung adenocarcinomas harbor an EML4-ALK gene fusion and define a unique tumor group that may be responsive to targeted therapy.
EML4_ALK- 22296236bronchioloalveolar carcinoma FISH - However, FISH studies failed to reveal EML4-ALK and KIF5B-ALK fusion genes in this BAC. /// "However, FISH studies failed to reveal EML4-ALK and KIF5B-ALK fusion genes in this BAC. " /// Small non-mucinous bronchioloalveolar carcinoma with anaplastic lymphoma kinase immunoreactivity: a novel ALK fusion gene? Echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (EML4-ALK) and kinesin family member 5B (KIF5B)-ALK are newly identified transforming fusion oncogenes causing non-small-cell lung cancers. /// Echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (EML4-ALK) and kinesin family member 5B (KIF5B)-ALK are newly identified transforming fusion oncogenes causing non-small-cell lung cancers.
EML4_ALK- 23664446non small cell lung cancer FISH - To the best of our knowledge, this is the first report concerning the presence of the EML4-ALK fusion gene in a sarcomatoid carcinoma of the lung. /// EML4-ALK rearrangement was detected with immunohistochemistry and confirmed with fluorescent in situ hybridization (FISH). /// EML4-ALK translocation in both metachronous second primary lung sarcomatoid carcinoma and lung adenocarcinoma: a case report.. /// " The EML4-ALK gene translocation was described in a non small cell lung cancer (NSCLC) subset, with a potent oncogenic activity. " /// "Starting from our evidence, tumors with sarcomatoid histology may need to be screened for the presence of EML4-ALK rearrangement." /// "Starting from our evidence, tumors with sarcomatoid histology may need to be screened for the presence of EML4-ALK rearrangement. "
EML4_ALK- 23325296non small cell lung cancer;lung cancer FISH - EML4-ALK fusion genes define a molecular subset of NSCLC with distinct clinical characteristic (lung adenocarcinoma, never or former smoker, usually mutually exclusive with EGFR mutations). /// "EML4-ALK fusion genes define a molecular subset of NSCLC with distinct clinical characteristic (lung adenocarcinoma, never or former smoker, usually mutually exclusive with EGFR mutations). " /// "Crizotinib has been shown to yield important clinical benefit such as objective response rate, progression-free survival (PFS), and anticipated improvements in quality of life when used in pretreated patients with advanced NSCLC harboring EML4-ALK gene rearrangement. "
EML4_ALK- 23576200non small cell lung cancer;lung cancer FISH;PCR - Clinical data have been generated for crizotinib, a small molecule inhibitor of the ALK receptor tyrosine kinase, demonstrating a substantial improvement of objective response rate and prolonged progression-free survival (PFS) compared to standard chemotherapy in pretreated NSCLC patients harbouring EML4-ALK fusion genes.
EML4_ALK- 23669200non small cell lung cancer;lung cancer FISH;PCR;RT-PCR - RT-PCR revealed the expression of an EML4-ALK fusion gene variant 1.
EML4_ALK- 26704831prostate cancer FISH - EML4-ALK fusion gene was not detected. /// The EML4-ALK fusion gene was not found in prostate cancer..
EML4_ALK- 23919423- FISH;PCR - Ten percent (11/110) of patients harbored the EML4-ALK fusion gene, and the frequency of ALK rearrangement was higher than that of other cohort analyses involving patients from other regions in China. /// "EGFR and KRAS mutations were examined by direct sequencing, the EML4-ALK fusion gene was analyzed by fluorescence in situ hybridization, and c-MET amplification and c-Met protein expression were detected by quantitative PCR and immunohistochemistry, respectively. " /// "Almost all of these gene mutations were exclusive except that in two female non-smoking patients, who harbored an EGFR mutation and EML4-ALK rearrangement simultaneously. " /// "We evaluated mutations in four driver genes, namely epidermal growth factor receptor (EGFR), Kirsten ras oncogene (KRAS), c-MET, and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), in Chinese lung adenocarcinoma patients from Hunan Province. " /// "Analysis of EGFR, EML4-ALK, KRAS, and c-MET mutations in Chinese lung adenocarcinoma patients.. "
EML4_ALK- 25839699non small cell lung cancer;lung cancer;adenocarcinoma FISH;PCR - Detection of EML4-ALK fusion gene in Chinese non-small cell lung cancer by using a sensitive quantitative real-time reverse transcriptase PCR technique.. /// "We identified 18 cases (10.4%) with EML4-ALK fusion-positive by qRT-PCR, and all were positive for EML4-ALK fusion gene validated by direct sequencing. " /// "Furthermore, of the 18 EML4-ALK fusion-positive cases, 16 (9.2%) were positive by using EML4-ALK fusion probe FISH, and 15 (8.7%) were positive by using ALK break-apart probe FISH and immunohistochemistry staining. " /// "QRT-PCR is a rapid, sensitive technology that could be used as a screening tool for identifying EML4-ALK fusion-positive NSCLC patients who would be sensitive for receiving ALK inhibitor therapy. "
EML4_ALK- 25708242non small cell lung cancer;lung cancer;adenocarcinoma FISH - The aim of this study is to better understand the clinical and molecular features of the EML4-ALK fusion gene in lung cancer patients in Taiwan and therefore to generate an efficient algorithm for the detection of ALK translocation. /// The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene is an important biomarker for target therapy. /// The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene is an important biomarker for target therapy.
EML4_ALK- 19737969colorectal cancer FISH - The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene has been identified as an oncogene in a subset of non-small cell lung cancers (NSCLC). /// "EML4-ALK translocation was also confirmed by fluorescence in situ hybridization assay, which revealed its substantial heterogeneity in both primary tumors and tumor-derived cell lines. " /// This approach led to the detection of EML4-ALK fusion in breast and colorectal carcinomas in addition to NSCLC. /// "To elucidate the functional significance of EML4-ALK, we examined the growth of cell lines harboring the fusion following EML4 and ALK silencing by small interfering RNA. " /// Besides previously known EML4-ALK variants 1 (E13. /// "Collectively, these findings show the recurrence of EML4-ALK fusion in multiple solid tumors and further substantiate its role in tumorigenesis.. " /// "Exon array profiling detects EML4-ALK fusion in breast, colorectal, and non-small cell lung cancers.. " /// "Screening of a large collection of patient tumor samples showed the presence of EML4-ALK fusion in 2.4% of breast (5 of 209), 2.4% of colorectal (2 of 83), and in 11.3% of NSCLC (12 of 106). "
EML4_ALK- 24792336non small cell lung cancer;lung cancer FISH;PCR - In one case of 96 EML4-ALK fusion gene and EGFR mutation were detected. /// TaqMan based real time PCR assay targeting EML4-ALK fusion transcripts in NSCLC.. /// "Using variant specific real time PCR we identified EML4-ALK transcript in 17/46 (37%) specimens, using end-point PCR in 13/46 (28%) specimens and positive ALK rearrangement by FISH was detected in 8/46 (17.4%) specimens. " /// This assay was used to analyze the EML4-ALK gene in 96 non-selected NSCLC specimens and compared with two other methods (end-point PCR and break-apart FISH). /// "EML4-ALK was detected in 33/96 (34%) specimens using variant specific real time PCR, whereas in only 23/96 (24%) using end-point PCR." /// "In this context, an effective method for EML4-ALK detection is necessary." /// "EML4-ALK was detected in 33/96 (34%) specimens using variant specific real time PCR, whereas in only 23/96 (24%) using end-point PCR. " /// "In this context, an effective method for EML4-ALK detection is necessary. "
EML4_ALK- 25238939lung cancer;adenocarcinoma FISH;PCR;RT-PCR - Moreover, RT-PCR using formalin-fixed, paraffin-embedded tissue from the right lung cancer also demonstrated EML4-ALK variant 1 fusion gene. /// Recurrence of lung adenocarcinoma after an interval of 15 years revealed by demonstration of the same type of EML4-ALK fusion gene.. /// "Moreover, RT-PCR using formalin-fixed, paraffin-embedded tissue from the right lung cancer also demonstrated EML4-ALK variant 1 fusion gene. " /// "Although there is a possibility that the left lung cancer is de novo one with multiple metastases, detection of the same fusion gene of the very rare EML4-ALK variant 1 in both tumors suggests that the left cancer is a recurrence of the right lung cancer after an interval of 15 years. " /// "Using the BAL specimen from the left lower lung, EML4 (echinoderm microtubule-associated protein-like 4)-ALK variant 1 fusion gene was detected by reverse transcription-polymerase chain reaction (RT-PCR). "
EML4_ALK- 25170107malignant pleural effusion;pleural effusion FISH - A new human lung adenocarcinoma cell line harboring the EML4-ALK fusion gene.. /// "To the best of our knowledge, there are only three cell lines harboring the EML4-ALK fusion gene, which have contributed to the development of therapeutic strategies. " /// We successfully established a new lung adenocarcinoma cell line harboring the EML4-ALK fusion gene. /// "Because the EML4-ALK rearrangement was found in a biopsied specimen using fluorescence in situ hybridization, she was treated with crizotinib." /// "Because the EML4-ALK rearrangement was found in a biopsied specimen using fluorescence in situ hybridization, she was treated with crizotinib. " /// "Therefore, we tried to establish a new lung cancer cell line harboring EML4-ALK. " /// "The EML4-ALK fusion protein and genes were identified in ABC-11 cells using fluorescence in situ hybridization and immunohistochemistry, respectively. "
EML4_ALK- 25601488non small cell lung cancer;lung cancer FISH;PCR;RT-PCR - However, a detailed RT-PCR analysis and sequencing revealed an unexpected 138 bp insertion of attractin-like 1 (ATRNL1) gene into the EML4-ALK fusion gene. /// "However, a detailed RT-PCR analysis and sequencing revealed an unexpected 138 bp insertion of attractin-like 1 (ATRNL1) gene into the EML4-ALK fusion gene. " /// Identification of atypical ATRNL1 insertion to EML4-ALK fusion gene in NSCLC.. /// "No EGFR mutations were detected, and therefore the ALK rearrangement was evaluated using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and the reverse transcription PCR (RT-PCR) method for EML4-ALK. " /// "This case shows great EML4-ALK heterogeneity and also that basic detection methods (IHC, FISH) cannot fully specify ALK rearrangement but in many cases a full specification seems to be important for an effective TKI indication, and sequencing ALK variants might contribute to optimized patient selection.. " /// "In our case, the positive therapeutic response suggests that ATRNL1 insertion does not affect EML4-ALK's sensitivity to crizotinib." /// We herein present a rare case of an EML4-ALK positive patient. /// "In our case, the positive therapeutic response suggests that ATRNL1 insertion does not affect EML4-ALK's sensitivity to crizotinib. "
EML4_ALK- 23625156non small cell lung cancer;lung cancer;adenocarcinoma FISH;PCR;RT-PCR - The echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) fusion gene has been identified as a potent oncogenic driver in non-small-cell lung cancer, in particular adenocarcinoma (ADC). /// "Two cases with positive ALK protein expression, but negative for breakapart FISH signal were shown to harbor EML4-ALK variant 1 by RT-PCR. " /// Detection of ALK rearrangement by immunohistochemistry in lung adenocarcinoma and the identification of a novel EML4-ALK variant.. /// "In addition, we identified a novel EML4-ALK fusion variant (E3:ins53A20), and its potent transformation potential has been confirmed by in vivo tumorigenicity assay. "
EML4_ALK- 24722159squamous cell carcinoma FISH - ALK/EML4 fusion gene may be found in pure squamous carcinoma of the lung..
EML4_ALKinv(2)(p21p23) / 18927303non small cell lung cancer;lung cancer FISH;PCR;RT-PCR - EML4-ALK is a fusion-type protein tyrosine kinase that is generated by inv(2)(p21p23) in the genome of non-small cell lung cancer (NSCLC). /// "To allow sensitive detection of EML4-ALK fusion transcripts, we have now developed a multiplex reverse transcription-PCR (RT-PCR) system that captures all in-frame fusions between the two genes. " /// Multiplex reverse transcription-PCR screening for EML4-ALK fusion transcripts.. /// "The novel isoforms of EML4-ALK manifested marked oncogenic activity, and they yielded a pattern of cytoplasmic staining with fine granular foci in immunohistochemical analysis of NSCLC specimens. " /// "The novel isoforms of EML4-ALK manifested marked oncogenic activity, and they yielded a pattern of cytoplasmic staining with fine granular foci in immunohistochemical analysis of NSCLC specimens."
EML4_ALK- 25706305non small cell lung cancer;lung cancer;adenocarc FISH - Here we present a meta-analysis of large-scale studies to evaluate the clinicopathological characteristics of NSCLC patients harboring the EML4-ALK fusion gene. /// Patients with the EML4-ALK fusion gene demonstrate unique clinicopathological and physiological characteristics. /// "The positive rate of the EML4-ALK fusion gene expression in females were slightly higher than that in males, but not significantly (P = 0.52). " /// "Additionally, the EML4-ALK fusion gene was exclusive of the EGFR and KRAS mutation genes. " /// Both English and Chinese databases were systematically used to search the materials of the clinicopathological characteristics of patients with NSCLC harboring the EML4-ALK fusion gene. /// "The correlation of the EML4-ALK fusion gene and clinicopathological characteristics of NSCLC patients demonstrated a significant difference in smoking status, histological types, stage, and ethnic characteristics. " /// "In addition, the EML4-ALK fusion gene was mutually exclusive of the EGFR and KRAS mutation genes (P = 0.00). " /// "Our pooled analysis revealed that the EML4-ALK fusion gene was observed predominantly in adenocarcinoma, non-smoking and NSCLC patients, especially those diagnosed in the advanced clinical stage of NSCLC. " /// Clinicopathological characteristics of patients with non-small-cell lung cancer who harbor EML4-ALK fusion gene: a meta-analysis.. /// The incidence rate of EML4-ALK fusion in NSCLC patients was found to be 6.8% (472/6950).
EML4_ALK- 26805736non small cell lung cancer;lung cancer FISH - IHC can be a simple and rapid way in screening EML4-ALK fusion gene mutation and exhibits important clinical values.. /// Figures showed that the disease control rate could reach up to 80% in NSCLC patients with EML4-ALK fusion gene after treated with ALK inhibitors. /// Immunohistochemical detection of EML4-ALK fusion gene mutation with specific antibody is feasible. /// Immunohistochemical detection of EML4-ALK fusion gene mutation with specific antibody is feasible. /// "Thus, exploring an accurate and rapid detecting method is the key in screening NSCLC patients with EML4-ALK expressions. " /// [Value of Immunohistochemical Methods in Detecting EML4-ALK Fusion Mutations: A Meta-analysis].. /// The aim of this study is to analyze the specificity and sensitivity of IHC in detecting EML4-ALK fusion mutations.
EML4_ALK- 21656749non small cell lung cancer;lung cancer FISH - It was recently reported in nonsmall cell lung cancer (NSCLC) that the fusion protein encoded by echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) fusion gene conferred oncogenic properties. /// Overexpression of the novel ALK fusion gene and variants 3a and 3b of EML4-ALK was performed to assess downstream signaling and functional effects. /// "The authors used 5' rapid amplification of complementary DNA ends to screen for potential, novel 5' fusion partners of ALK other than EML4-ALK. "
EML4_ALK- 22124476malignant pleural effusion FISH;PCR - In addition, K-ras mutation was analyzed for patients without EML4-ALK fusion genes. /// There were 39 patients (34%) with the EML4-ALK fusion gene. /// The K-ras mutation rate for patients without EML4-ALK fusion gene was 6.5%. /// "Comparing patients with tumors harboring variant 1 with those harboring nonvariant 1 EML4-ALK fusion genes, there were no significant differences in clinical factors and survival outcome. " /// "For lung adenocarcinoma patients with wild-type EGFR, EML4-ALK translocation is associated with longer overall survival.. " /// EML4-ALK translocation predicts better outcome in lung adenocarcinoma patients with wild-type EGFR.. /// "By multivariate analysis, patients who had better performance status (p < 0.001) and EML4-ALK translocation (p = 0.017) had longer overall survival. " /// "For lung adenocarcinoma patients with wild-type EGFR, EML4-ALK translocation is associated with longer overall survival.." /// Lung adenocarcinoma patients with malignant pleural effusions having wild-type EGFR and measurable target lesions were enrolled for EML4-ALK analysis by reverse transcription-polymerase chain reaction and direct sequencing. /// "To understand the impact of EML4-ALK on the prognosis of non-small cell lung cancer, we examined EML4-ALK fusion in lung adenocarcinoma from patients with wild-type EGFR and analyzed their clinical treatment outcomes. " /// "To understand the impact of EML4-ALK on the prognosis of non-small cell lung cancer, we examined EML4-ALK fusion in lung adenocarcinoma from patients with wild-type EGFR and analyzed their clinical treatment outcomes." /// "Demographic data, EML4-ALK status, and survival data were analyzed. " /// "Demographic data, EML4-ALK status, and survival data were analyzed." /// EML4-ALK fusion is mutually exclusive with epidermal growth factor receptor (EGFR) mutations. /// " The echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion represents a novel target in a subset of non-small cell lung cancer, especially adenocarcinoma. " /// "The echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion represents a novel target in a subset of non-small cell lung cancer, especially adenocarcinoma."
EML4_ALK- 22879549lung cancer;adenocarcinoma FISH - We previously reported clinicopathological findings of patients with lung cancer harboring the EML4-ALK fusion gene. /// EML4-ALK was detected by a reverse transcription polymerase-chain reaction and by the newly established criteria and algorithm using a fluorescence in situ hybridization method. /// EML4-ALK was detected by a reverse transcription polymerase-chain reaction and by the newly established criteria and algorithm using a fluorescence in situ hybridization method. /// We investigated EML4-ALK in tumors from 581 patients. /// To develop an easy-to-use technique for EML4-ALK detection and establish the effective selection of candidates for screening. /// "Of the 27 patients, 8 (29.6%) had EML4-ALK. " /// "8 (1.3%) tumors had EML4-ALK, EGFR, KRAS, and ERBB2 mutations, which were mutually exclusive and were detected in 191 (32.8%), 56 (9.6%), and 11 (1.8%) tumors, respectively. " /// "Anaplastic lymphoma kinase inhibitors have therapeutic effects in lung cancer patients with EML4-ALK, accounting for merely 1%-5% of lung cancers. "
EML4_ALK- 23856136mesothelioma FISH - Fluorescence in situ hybridization (FISH) was performed to detect EML4-ALK gene rearrangement. /// "Clinical and pathological data were collected, including age, gender, smoking status, treatment, response, and molecular biomarkers such as thymidylate synthetase (TS) expression, echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) gene rearrangement." /// EML4-ALK gene rearrangement was studied in 32 patients and 6 (18.8%) were positive. /// "Clinical and pathological data were collected, including age, gender, smoking status, treatment, response, and molecular biomarkers such as thymidylate synthetase (TS) expression, echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) gene rearrangement. " /// "Correlation between TS expression or EML4-ALK rearrangement and outcome of pemetrexed-based chemotherapy for MPM may contribute to future individualized treatment, which needs further validation from large-scale prospective studies.." /// "Correlation between TS expression or EML4-ALK rearrangement and outcome of pemetrexed-based chemotherapy for MPM may contribute to future individualized treatment, which needs further validation from large-scale prospective studies.. "
EML4_ALK- 26142544non small cell lung cancer;lung cancer FISH;PCR - Sixteen patients were detected with low copy numbers of EML4-ALK gene rearrangement, which failed to meet the positive cutoff point of FISH. /// "Three variants (1, 2, and 3) of the EML4-ALK gene rearrangements were detected. " /// Our study indicates that ddPCR can be used as a molecular analytical tool to accurately measure the EML4-ALK rearrangement copy numbers in FFPE samples of lung adenocarcinoma patients.
EML4_ALK- 21921848lung cancer;adenocarcinoma FISH - A subset of lung cancers harbors an EML4-ALK (echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase) gene fusion, and detecting this subset may hold therapeutic implications. /// We examined 15 lung adenocarcinomas with reverse-transcriptase polymerase chain reaction-proven EML4-ALK fusion transcripts and 30 ALK-negative cases.
EML4_ALK- 25144242non small cell lung cancer;lung cancer FISH - Although EML4-ALK is reported to be formed by inversion of chromosome 2, other mechanisms of this gene fusion remain unknown. /// This study aimed to examine the mechanism of EML4-ALK rearrangement using a novel cell line with the EML4-ALK fusion gene. /// "These observations provided the first evidence that EML4-ALK fusion in JFCR-LC649 cells was formed in chromosome 2 by a distinct mechanism of genomic rearrangement, termed chromothripsis. " /// A novel mechanism of EML4-ALK rearrangement mediated by chromothripsis in a patient-derived cell line.. /// Our results suggested that chromothripsis may be a mechanism of oncogenic rearrangement of EML4-ALK. /// EML4-ALK is a driver oncogene in non-small-cell lung cancer (NSCLC) and has been developed into a promising molecular target for antitumor agents.
EML4_ALK- 24156086inflammatory breast carcinoma FISH - FISH analysis showed no EML4-ALK gene rearrangement in any samples, although 16 of the 25 samples (64%) contained 3 to 4 extra copies of the ALK gene, and chromosome 2 aneusomy was found in 7 of 8 samples that had extra copies of the ALK gene.
EML4_ALK- 23891510non small cell lung cancer;lung cancer;adenocarcinoma FISH - KIF5B/RET fusion gene analysis in a selected series of cytological specimens of EGFR, KRAS and EML4-ALK wild-type adenocarcinomas of the lung.. /// "This transforming gene arise from the fusion of KIF5B and the RET proto-oncogene, and it is mutually exclusive with EGFR, KRAS and EML4/ALK alterations. "
EML4_ALK- 25898958non small cell lung cancer FISH - The standard diagnostic method for echinoderm microtubule-associated protein-like 4-anaplastic lymphoma receptor tyrosine kinase translocation is fluorescence in situ hybridization (FISH).
EML4_ALK- 25847523small cell lung cancer;lung cancer FISH - The ALK/EML4 TriCheck FISH probe may be useful for the detection of ALK rearrangements, especially in borderline or atypical cases, where an additional unique ALK FISH probe may provide further confirmation of rearrangement.. /// ALK FISH was prospectively performed on 45 NSCLCs with the ALK/EML4 TriCheck probe (ZytoVision) and the Vysis ALK break-apart probe (Abbott Molecular). /// The aim of this study was to evaluate the ALK/EML4 TriCheck FISH probe in a series of NSCLCs enriched for tumours with equivocal ALK status.
EML4_ALK- 19147828non small cell lung cancer;lung cancer FISH;PCR - A fusion gene, echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK), with transforming activity has recently been identified in a subset of non-small cell lung cancer (NSCLC), but its pathogenetic, diagnostic, and therapeutic roles remain unclear. /// "In cases carrying the fusion transcript, we determined EML4-ALK gene and protein levels using fluorescence in situ hybridization, Western blotting, and immunoprecipitation. " /// EML4-ALK rearrangement in non-small cell lung cancer and non-tumor lung tissues.. /// Fluorescence in situ hybridization analysis of cases expressing EML4-ALK transcripts showed that only a minority of cells harbored the EML4-ALK gene. /// The EML4-ALK transcript cannot be regarded as a specific diagnostic tool for NSCLC. /// Both frequency and type of EML4-ALK transcripts were investigated by reverse transcription PCR in 120 frozen NSCLC specimens from Italy and Spain. /// EML4-ALK transcripts (variants 1 and 3) were detected in 9 of 120 NSCLC samples but were not specific for NSCLC since they were also found in non-cancerous lung tissues taken far from the tumor. /// Our results show therefore that the causal role and value of EML4-ALK as a therapeutic target remain to be defined.. /// "None of these cases was found to express the EML4-ALK protein as examined by immunohistochemistry, Western blotting, and immunoprecipitation. "
EML4_ALK- 23198868non small cell lung cancer;lung cancer;adenocarcinoma FISH;PCR;RT-PCR - Five of 8 patients with ALK rearrangements detected by FISH were confirmed to have EML4-ALK fusions by multiplex RT-PCR.
EML4_ALK- 20935334lung cancer;adenocarcinoma FISH - A subset of lung cancers harbours the fusion gene echinoderm microtubule-associated protein-like-4-anaplastic lymphoma kinase (EML4-ALK). /// The combined use of morphological feature analysis and immunohistochemistry may be a useful and cost effective screening method for EML4-ALK lung adenocarcinoma..
EML4_ALK- 23536384lung cancer;adenocarcinoma FISH - Reverse transcriptase-polymerase chain reaction analysis of this CB revealed the presence of an EML4-ALK rearrangement, thereby confirming a false-negative FISH result in the CB.
EML4_ALK- 22610646breast cancer;adenocarcinoma FISH - In addition, a tissue microarray was constructed to screen for EGFR gene copy gain and EML4-ALK fusion by FISH. /// "In addition, a tissue microarray was constructed to screen for EGFR gene copy gain and EML4-ALK fusion by FISH. "
EML4_ALKinv(2) / 26172300colorectal carcinoma;adenocarcinoma FISH - One out of 50 CRC patients enrolled in a pathway-directed therapeutic trial was ALK IHC positive (3+) confirmed by ALK FISH and found to harbor the EML4-ALK (E21, A20) fusion variant by CGP. /// "One out of 50 CRC patients enrolled in a pathway-directed therapeutic trial was ALK IHC positive (3+) confirmed by ALK FISH and found to harbor the EML4-ALK (E21, A20) fusion variant by CGP." /// Growth of a tumor cell line derived from this EML4-ALK CRC patient was inhibited by ALK inhibitors crizotinib and entrectinib.
EML4_ALK- 25806283non small cell lung cancer;lung cancer;adenocarcinoma FISH;PCR;RT-PCR - In our experience, reverse transcription polymerase chain reaction (RT-PCR)-based detection of EML4-ALK is a more sensitive and reliable approach compared to FISH and immunohistochemistry (IHC). /// "Concordance of IHC, FISH and RT-PCR for EML4-ALK rearrangements.. " /// "In our experience, reverse transcription polymerase chain reaction (RT-PCR)-based detection of EML4-ALK is a more sensitive and reliable approach compared to FISH and immunohistochemistry (IHC). " /// The echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) has emerged as the second most important driver oncogene in lung cancer and the first targetable fusion oncokinase to be identified in 4-6% of lung adenocarcinomas.
EML4_ALK- 23533259non small cell lung cancer;lung cancer FISH - One patient with an EGFR mutation also showed an EML4-ALK translocation, and both FISH-positive and FISH-negative cells maintained the EGFR mutation. /// EGFR mutation analysis can be performed on the same sample previously submitted to the EML4-ALK FISH procedure.. /// Molecular determinations of EGFR and EML4-ALK on a single slide of NSCLC tissue.. /// "FISH analysis was performed on one cytological or histological sample to determine EML4-ALK status, after which the same cells scraped off each slide were used to evaluate the EGFR status. "
EML4_ALK- 21757253non small cell lung cancer;lung cancer;adenocarcinoma FISH;PCR;RT-PCR - The echinoderm microtubule-associated protein-like 4(EML4)-ALK or kinesin family member 5B (KIF5B)-ALK translocation was confirmed by the reverse transcription polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH). /// "Out of 404 cases, there were 14 of EML4-ALK non-small cell carcinoma (NSCLC) and one KIF5B-ALK NSCLC case (8 men, 7 women. " /// The powerful effect of ALK inhibitor on EML4-ALK NSCLC was observed. /// The ALK inhibitor presented in this study is effective in EML4-ALK NSCLC cases.
EML4_ALK- 26352533non small cell lung cancer;lung cancer FISH;PCR;RT-PCR - EML4-ALK Fusion Detected by RT-PCR Confers Similar Response to Crizotinib as Detected by FISH in Patients with Advanced Non-Small-Cell Lung Cancer..
EML4_ALK- 23453647large cell carcinoma FISH - ALK translocation status was constant between BM and primary tumors in 16 evaluable cases including two cases with ALK-EML4 translocations Among these 16 cases ALK amplification was seen in two BM and none of the primary tumors.
EML4_ALK- 25757141non small cell lung cancer;lung cancer FISH - Of these 115 samples, 79 (69%) were negative for echinoderm microtubule-associated protein like 4 (EML4)-ALK translocation, nine (8%) were positive and 27 (23%) were unevaluable.
EML4_ALK- 24992173colorectal carcinoma;lung cancer;adenocarcinoma FISH - Recently, small studies of colorectal carcinomas (CRCs) have suggested an incidence of EML4-ALK translocations of 0.4% to 2.4% and FIG-ROS1 translocations of 0.8%.
EML4_ALK- 25755678gastrointestinal cancer;signet ring cell carcinoma FISH - ALK-EML4 translocation is an established driver aberration in non-small cell lung cancer (NSCLC), with reported predilection for cases with signet ring histology.
EML4_ALK- 24999991breast cancer FISH - Blood samples were completely separated into plasma, CTCs and PBMCs components and each fraction were characterized with immunophenotyping (Pan-cytokeratin/CD45, CD44/CD24, EpCAM), fluorescence in-situ hybridization (FISH) (EML4-ALK) or targeted somatic mutation analysis. /// "Blood samples were completely separated into plasma, CTCs and PBMCs components and each fraction were characterized with immunophenotyping (Pan-cytokeratin/CD45, CD44/CD24, EpCAM), fluorescence in-situ hybridization (FISH) (EML4-ALK) or targeted somatic mutation analysis. "
EML4_ALK- 20228600lung cancer;adenocarcinoma FISH - On the other hand, the commercially available chromosomal fluorescent in situ hybridization (FISH) analysis showed split signals of ALK, which was confirmed to be the EML4-ALK inversion.
EML4_ALK- 23887300adenocarcinoma FISH;PCR - EGFR alterations and EML4-ALK rearrangement in primary adenocarcinoma of the urinary bladder. /// EGFR alterations and EML4-ALK rearrangement in primary adenocarcinoma of the urinary bladder..
EML4_ALK- 25721120lung cancer FISH - The FISH-based method of detecting EML4-ALK rearrangement in lung cancer may miss a significant number of patients who could benefit from targeted ALK therapy. /// Food and Drug Administration-approved method for detecting EML4-ALK rearrangement is fluorescence in situ hybridization (FISH). /// "We studied FISH and IHC (D5F3 antibody) systematically for EML4-ALK rearrangement in 51 lung adenocarcinoma patients, followed by NGS in case of discordance. " /// "Screening for EML4-ALK rearrangement by IHC should be strongly considered, and NGS is recommended in borderline cases. " /// "Fluorescence in situ hybridization, immunohistochemistry, and next-generation sequencing for detection of EML4-ALK rearrangement in lung cancer.. "
EML4_ALK- 24742568adenoid cystic carcinoma FISH - To evaluate the sensitivity and specificity of fully automated immunohistochemistry (IHC), with comparison to FISH, in the detection of EML4-ALK rearrangement in lung adenocarcinoma (ADC).
EML4_ALK- 24942894non small cell lung cancer;lung cancer FISH - Variations in molecular profile in NSCLC can be analyzed using cytological samples: development of EGFR resistance mutations and coexistence of ALK-EML4 translocation in an EGFR-sensitive patient.. /// "At this point, fluorescence in situ hybridization also detected ALK-EML4 translocation. " /// "To our knowledge, this is the first case reported with these characteristics, and the 11th case described with coexistence of EGFR mutations and ALK-EML4 rearrangements. " /// We report a case of a non-small cell lung carcinoma patient with coexistence of EGFR mutations and ALK-EML4 rearrangements that responded to EGFR inhibitors and in which the development of a new resistance mutation in exon 20 of EGFR-determined treatment resistance.
EML4_ALK- 22706607non small cell lung cancer;adenocarcinoma FISH - Here, we report a novel EML4-ALK variant detected by reverse transcription polymerase chain reaction analysis. /// "Therefore, the different EML4-ALK variants so far contain the same 3' portion of ALK starting with exon 20. " /// A novel EML4-ALK variant: exon 6 of EML4 fused to exon 19 of ALK.. /// Subsequent sequencing revealed an EML4-ALK fusion variant in which exon 6 of EML4 was fused to exon 19 of ALK.
EML4_ALK- 24756793non small cell lung cancer;lung cancer FISH - There is convincing clinical evidence for the effectiveness in non-small-cell lung cancer (NSCLC) harboring EML4-ALK rearrangements resulting in constitutional activation of the ALK-RTK.
EML4_ALK- 23561899non small cell lung cancer;lung cancer FISH - Crizotinib is a small orally-administered ALK inhibitor for patients with non-small cell lung cancer with EML4-ALK rearrangement (echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase).
EML4_ALK- 26268359adenocarcinoma FISH;PCR;RT-PCR - The KIF5B-RET rearrangement is detected with the frequency of 1??~??2% in 'triple marker'-negative lung adenocarcinomas, i.e., EGFR, KRAS and EML4-ALK wild type.
EML4_ALK- 23979196non small cell lung cancer;lung cancer FISH - EML4-ALK demonstrates constitutive kinase activity.
EML4_ALK- 26678488colorectal cancer;gastric cancer;lung cancer;esophageal cancer FISH;PCR - By qRT-PCR, EML4-ALK fusion was found in one IHC-positive CRC case.
EML4_ALK- 22153831lung cancer;adenocarcinoma FISH;PCR;RT-PCR - EML4-ALK adenocarcinomas constitute a new molecular subgroup of lung tumours that respond very well to crizotinib, an ALK inhibitor.
EML4_ALK- 26391021squamous cell carcinoma;lung cancer;adenocarcinoma FISH - No discrepancies in EML4-ALK rearrangements existed according to fluorescence in situ hybridization. /// Rare ITHs of EGFR/KRAS/EML4-ALK alterations within histologically heterogeneous primary lung adenocarcinomas existed by methods with higher sensitivity. /// "Driver genes, epidermal growth factor receptor (EGFR), KRAS and EML4-ALK, were assessed by assays with different sensitivities. " /// EML4-ALK=4) were enrolled.
EML4_ALK- 21107285non small cell lung cancer;non small cell lung cancer;lung cancer;adenocarcinoma FISH - There were two cases of EML4-ALK translocation and one with an atypical translocation of ALK. /// "In conclusion, EML4-ALK translocation is a rare event in NSCLC. " /// "Both cases of EML4-ALK translocation had ALK protein expression, whereas in the rest, ALK was undetected. "
EML4_ALK- 26984109non small cell lung cancer;lung cancer FISH - Immunohistochemical techniques to identify and screen for EML4-ALK translocations may play an important role in the near future. /// Treatment options such as tyrosine kinase inhibitors directed against the EML4-ALK signalling pathway lead to improved progression free and overall survival. /// The EML4-ALK pathway plays an important role in a significant subset of non-small cell lung cancer patients.
EML4_ALK- 26295973sarcoma;thyroid cancer FISH;PCR - Our results suggest that the EML4-ALK fusion in MTC may be a potential driver mutation and a valid target of ALK inhibitors. /// "Notably, a metastatic MTC case harboring the EML4-ALK fusion showed a dramatic response to an ALK inhibitor, crizotinib. " /// Glutamine:fructose-6-phosphate transaminase 1 (GFPT1)-ALK and echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusions were identified.
EML4_ALK- 24992725non small cell lung cancer;lung cancer FISH;PCR;RT-PCR - EML4-ALK is a new driver gene of non-small cell lung cancer and a target of crizotinib.
EML4_ALK- 25723109lung cancer FISH - EML4-ALK inversion and ROS1 fusions emerge as common fusion abnormalities in IMT, closely recapitulating the pattern seen in lung cancer. /// "In addition, next-generation paired-end RNA sequencing and FusionSeq algorithm was applied in 4 cases, which identified EML4-ALK fusions in 2 cases." /// "Of note, EML4-ALK inversion was noted in 7 (20%) cases, seen mainly in the lung and soft tissue of young children including 2 lesions from newborns. " /// "In addition, next-generation paired-end RNA sequencing and FusionSeq algorithm was applied in 4 cases, which identified EML4-ALK fusions in 2 cases. " /// "EML4-ALK inversion and ROS1 fusions emerge as common fusion abnormalities in IMT, closely recapitulating the pattern seen in lung cancer. "
EML4_ALK- 24846683- FISH - EML4-ALK was evaluated using immunohistochemistry and fluorescence in situ hybridization, and EGFR mutations were analyzed using the Cycleave method. /// "EML4-ALK was evaluated using immunohistochemistry and fluorescence in situ hybridization, and EGFR mutations were analyzed using the Cycleave method."
EML4_ALK- 22347464lung cancer FISH - We developed a 5'-rapid amplification of cDNA ends-based system optimized for FFPE tissues and evaluated this system on a lung cancer tissue with ALK rearrangement and without the 2 known ALK fusions EML4-ALK and KIF5B-ALK.
EML4_ALK- 22722791non small cell lung cancer;non small cell lung cancer;small cell lung c FISH - The assay also detected EML4-ALK variants 1 or 3 in three FFPE samples of surgically resected NSCLC shown to be positive for anaplastic lymphoma kinase rearrangement by fluorescence in situ hybridization. /// "We developed an assay system for the detection of EML4-ALK variants 1, 2, 3a, 3b, 4, 5a, 5b, 6, or 7 transcripts in total RNA obtained from formalin-fixed, paraffin-embedded (FFPE) specimens of NSCLC tissue. " /// "However, the currently available assays for the detection of the different variants of EML4-ALK have limitations. " /// Evaluation of the analytic sensitivity of the assay with serial dilutions of plasmids containing EML4-ALK complementary DNA sequences revealed it to be capable of the reliable detection of one copy of each plasmid per reaction. /// "Furthermore, the assay identified variant 1 of EML4-ALK in 3 of 20 FFPE biopsy samples from patients with advanced NSCLC. " /// Our novel assay is highly sensitive and effective for the detection of EML4-ALK in FFPE specimens.. /// The assay is based on region-specific polymerase chain reaction amplification of EML4-ALK complementary DNA followed by specific single-base primer extension and analysis of the extension products by matrix-assisted laser desorption/ionization-time of flight mass spectrometry.
EML4_ALK- 24346098squamous cell carcinoma FISH - Preselection based on clinical characteristics in German non-small-cell lung cancer patients screened for EML4-ALK translocation.. /// EML4-ALK positive patients seem to have distinct clinical features and show long responses to a number of systemic therapies.. /// We present the results of clinical preselection before EML4-ALK testing in a German NSCLC cohort. /// "EML4-ALK fusion is uncommon, reported in about 5% of NSCLC patients. " /// 16.4% of patients were positive for EML4-ALK fusion.
EML4_ALK- 24885803non small cell lung cancer;lung cancer FISH - Echinoderm microtubule associated proteinlike 4-anaplastic lymphoma receptor tyrosine kinase (EML4-ALK) translocation has been described in a subset of patients with non-small cell lung cancer (NSCLC) and has been shown to have oncogenic activity. /// "We also performed a MassARRAY-based analysis (Sequenom, San Diego, California) in a small subset of 11 samples to detect EML4-ALK rearrangement. " /// "In the 2 discrepant cases, we did not detect any mass peaks for the EML4-ALK variants by MassARRAY. "
EML4_ALK- 24638510non small cell lung cancer FISH - In this series, resected tumors from NSCLC patients at single center were detected for mutation in EGFR, as well as KRAS, BRAF, HER2, EML4-ALK and PIK3CA.
EML4_ALK- 23201355non small cell lung cancer;B cell lymphoma;anaplastic large cell lymphoma;lung cancer;neuroblastoma FISH - It is remarkable that the EML4-ALK fusion protein was discovered in 2007 and crizotinib was approved for the treatment of ALK-positive non-small cell lung cancer in 2011, which is a remarkably short timeframe in the overall scheme of drug discovery.. /// The EML4-ALK fusion protein and four other ALK-fusion proteins play a fundamental role in the development in about 5% of non-small cell lung cancers. /// About 28% of the cases of crizotinib resistance are related to nearly a dozen different mutations of ALK in the EML4-ALK fusion protein. /// "It is remarkable that the EML4-ALK fusion protein was discovered in 2007 and crizotinib was approved for the treatment of ALK-positive non-small cell lung cancer in 2011, which is a remarkably short timeframe in the overall scheme of drug discovery.. "
EML4_ALK- 24346090non small cell lung cancer;lung cancer;adenocarc FISH;PCR;RT-PCR - Large-scale screening and molecular characterization of EML4-ALK fusion variants in archival non-small-cell lung cancer tumor specimens using quantitative reverse transcription polymerase chain reaction assays.. /// "This panel of variant-specific, quantitative RT-PCR assays detects common EML4-ALK+ variants as well as ALK gene expression level in archival formalin-fixed paraffin-embedded NSCLC specimens." /// ALK expression level varied significantly among different EML4-ALK+ variants and individual tumors.
EML4_ALKinv(2)(p21;p23) / 19170230adenosquamous carcinoma - - The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene resulting from the chromosome inversion inv(2)(p21;p23) recently was identified in nonsmall cell lung cancer (NSCLC). /// The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS.. /// The EML4-ALK fusion gene was present in various histologic types of NSCLC. /// Thirteen tumors (4.9%) had EML4-ALK comprising 4 fusion transcript variants with fusion of the variable segments from 5' EML4 to 3' ALK and with preservation of the ALK kinase domain. /// "EML4-ALK was investigated in 266 resected primary NSCLC, including adenocarcinomas (AD), lymphoepithelioma-like carcinomas, squamous cell carcinomas, mucoepidermoid carcinomas, and adenosquamous carcinomas, by reverse transcriptase-polymerase chain reaction and was verified by sequencing. " /// EML4-ALK protein expression was studied by immunohistochemistry. /// "The authors of this study investigated the frequency, genetic and clinicopathologic profiles of EML4-ALK in Chinese patients with NSCLC. " /// The authors concluded that EML4-ALK may be useful for predicting the potential response to ALK inhibitors as a therapeutic option for patients with lung cancer.. /// EML4-ALK was associated with nonsmokers (P = .009). /// "EML4-ALK was investigated in 266 resected primary NSCLC, including adenocarcinomas (AD), lymphoepithelioma-like carcinomas, squamous cell carcinomas, mucoepidermoid carcinomas, and adenosquamous carcinomas, by reverse transcriptase-polymerase chain reaction and was verified by sequencing."
EML4_ALK- 25929953lung cancer - - The EML4-ALK gene fusion is detected in 4-8% of all lung cancers, predominantly in light smokers or nonsmokers.
EML4_ALK- 26766993non small cell lung cancer;lung cancer - - EML4-ALK gene fusion was tested in 43.9% (127/289) of NSCLC patients, and 98.4% (125/127) showed conclusive results: 6.4% (8/125) of those had gene fusion.
EML4_ALK- 23928533non small cell lung cancer;squamous cell carcinoma;non small cell lung cancer PCR - Female, non-smoker and adenocarcinoma histological subtype tend to be associated with a higher rate of EML4-ALK gene fusion.. /// "Female, non-smoker and adenocarcinoma histological subtype tend to be associated with a higher rate of EML4-ALK gene fusion.. " /// [Detection of EML4-ALK fusion gene in non-small cell lung cancer and its clinicopathologic correlation].. /// " To investigate the frequency of EML4-ALK fusion gene in non-small-cell lung cancer (NSCLC) patients, and its correlation with clinicopathologic features. " /// EML4-ALK fusion gene was found in 4.1% (11/268) of the cases. /// Chinese NSCLC patients have a 4.1% detection rate of EML4-ALK fusion gene in the tumor tissues. /// Real-time PCR was used to detect the presence of EML4-ALK fusion gene in 268 cases of NSCLCs using paraffin-embedded tissue samples(among which 164 samples were re-validated by Sanger sequencing).
EML4_ALK- 26829319adenocarcinoma - - We also resolve the structure of the EML4-ALK gene fusion in the NCI-H2228 cancer cell line using phased exome sequencing.
EML4_ALK- 25785456malignant pleural effusion FISH;PCR;RT-PCR - The EML4-ALK fusion gene status was determined with fluorescent in situ hybridization (FISH), reverse transcription-polymerase chain reaction (RT-PCR), and immunohistochemistry (IHC). /// "The EML4-ALK fusion gene status was determined with fluorescent in situ hybridization (FISH), reverse transcription-polymerase chain reaction (RT-PCR), and immunohistochemistry (IHC). " /// We attempted to clarify the feasibility of detecting the EML4-ALK fusion gene in pleural effusion cells using different methods. /// We attempted to clarify the feasibility of detecting the EML4-ALK fusion gene in pleural effusion cells using different methods. /// These results suggest that a block of pleural effusion cells can be used to detect the EML4-ALK fusion gene. /// "Detection of EML4-ALK in lung adenocarcinoma using pleural effusion with FISH, IHC, and RT-PCR methods." /// "Detection of EML4-ALK in lung adenocarcinoma using pleural effusion with FISH, IHC, and RT-PCR methods.. " /// RT-PCR is a good candidate method for detecting EML4-ALK in blocks of pleural effusion cells from lung cancer patients. /// EML4-ALK was detected in three of 66 patient samples (4.5%) with RT-PCR.
EML4_ALK- 25581823non small cell lung cancer;lung cancer - - In this study, we found that the lung adenocarcinoma cell line A925L expresses an EML4-ALK gene fusion (variant 5a, E2:A20) and is sensitive to the ALK inhibitors crizotinib and alectinib. /// "We further established highly tumorigenic A925LPE3 cells, which also have the EML4-ALK gene fusion (variant 5a) and are sensitive to ALK inhibitors. " /// Our in vivo imaging models of multiple organ sites may provide useful resources to analyze further the pathogenesis of EML4-ALK lung cancer and its response and resistance to ALK inhibitors in various organ microenvironments. /// "To investigate the molecular mechanism underlying tumor progression and targeted drug sensitivity/resistance in EML4-ALK lung cancer, clinically relevant animal models are indispensable. " /// "By using A925LPE3 cells with luciferase gene transfection, we established in vivo imaging models for pleural carcinomatosis, bone metastasis, and brain metastasis, all of which are significant clinical concerns of advanced EML4-ALK lung cancer. " /// EML4-ALK lung cancer accounts for approximately 3-7% of non-small-cell lung cancer cases.
EML4_ALK- 23372947non small cell lung cancer;lung cancer;adenocarcinoma - - Five out of 7 EGFR mutation-negative patients showed positive results for EML4-ALK gene fusion. /// Driver oncogene including EGFR mutation and EML4-ALK fusion gene was identified in 9 of 12 cases (75%). /// "Twelve patients with lung adenocarcinoma aged 40 or younger at Juntendo University Urayasu Hospital or Juntendo University Hospital from July 2004 to March 2010 were analyzed for driver oncogene status including EGFR activating mutation, EML4-ALK fusion gene, and K-ras mutation. "
EML4_ALK- 26332764lung cancer;adenocarcinoma - - Six of 22 (27.2%) cases contained EML4-ALK gene fusions. /// Six of 22 (27.2%) cases contained EML4-ALK gene fusions.
EML4_ALK- 18242762non small cell lung cancer;adenocarcinoma PCR;RT-PCR - EML4-ALK gene fusions have recently been discovered in a subset of human lung carcinomas, and fusions of the ALK tyrosine kinase gene with the NPM, TPM3, CLTC, ATIC, and TFG genes have been found in hematological malignancies. /// In situ PCR of a paraffin block section showed that the carcinoma with expression of the variant 1 actually contained an EML4-ALK fusion gene. /// These results suggested that the EML4-ALK fusion gene product is involved in the carcinogenesis of a subset of NSCLCs.. /// "No somatic mutations were detected in the mutation cluster regions of the EGFR, K-RAS, and PIK3CA genes in these two carcinomas, however, a Pro177Ser mutation of the p53 gene was detected in the carcinoma that contained the variant 1 EML4-ALK fusion transcripts. " /// "EML4-ALK fusion transcripts, but no NPM-, TPM3-, CLTC-, ATIC-, or TFG-ALK fusion transcripts, in non-small cell lung carcinomas.. " /// "Although no expression of NPM-, TPM3-, CLTC-, ATIC-, or TFG-ALK fusion transcripts were detected in any of the cases, expression of EML4-ALK fusion transcripts was detected in two (2.6%) of the 77 NSCLCs. " /// "Although no expression of NPM-, TPM3-, CLTC-, ATIC-, or TFG-ALK fusion transcripts were detected in any of the cases, expression of EML4-ALK fusion transcripts was detected in two (2.6%) of the 77 NSCLCs."
EML4_ALK- 22707299lung cancer;adenocarcinoma - - Previous studies have revealed that EGFR mutation and/or EML4-ALK gene fusion rate was higher in the non-smoker Asian females with pulmonary adenocarcinoma. /// "104 consecutively resected lung adenocarcinomas from 396 non-smoker females (less than 100 cigarettes in a lifetime) at a single institution (Tongji University, Shanghai, China) were analyzed for mutations in EGFR, EML4-ALK, KRAS, HER2, BRAF, and PIK3CA. " /// "A majority of the mutations were mutually exclusive, except two with EGFR mutation and BRAF mutation, one with EML4-ALK fusions and PI3K mutation. " /// "10 (9.6 %) harbored EML4-ALK fusions, two harbored KRAS mutations, two harbored BRAF mutations, and two harbored PI3K mutations. "
EML4_ALK- 26200269mucinous carcinoma - - Within the KRAS-negative cases, we found numerous potentially targetable gene fusions and mutations, including CD74-NRG1, VAMP2-NRG1, TRIM4-BRAF, TPM3-NTRK1, and EML4-ALK gene fusions and ERBB2, BRAF, and PIK3CA mutations.
EML4_ALK- 23675251- FISH;PCR;RT-PCR - Identification of Novel Variant of EML4-ALK Fusion Gene in NSCLC: Potential Benefits of the RT-PCR Method.. /// Here we present a novel variant of the EML4-ALK fusion gene which we named variant 3c. /// "RNA extracted from formalin fixed paraffin embedded (FFPE) specimens from patients with advanced and metastatic NSCLC was amplified, using primers and probes designed to detect specific EML4-ALK fusion gene fragments. " /// "Compared to FISH technology, RT-PCR enables the detection of different isoforms of the EML4-ALK transforming gene, which can be validated by sequencing. " /// "However, the clinical implications of the 15 different variants of the EML4-ALK transforming gene described so far are currently not defined. "
EML4_ALK1p34.3 / 7p21.1 / 16p13.3 / 9p21.3 / 9p23-24.1 / 23289484adenocarcinoma - - A subset of lung adenocarcinomas harboring an EML4-ALK fusion gene resulting in dominant oncogenic activity has emerged as a target for specific therapy. /// EML4-ALK fusion confers a characteristic histology and is detected more frequently in never or light smokers and younger patients.
EML4_ALKt(2;5)(p23;q35) / inv(2)(p21;p23) / 25727400non small cell lung cancer;anaplastic large cell lymphoma;small cell lu - - About 80% of ALK-positive anaplastic large-cell lymphoma (ALCL) cases are characterized by the t(2;5)(p23;q35) translocation, encoding for the aberrant fusion protein nucleophosmin (NPM)-ALK, whereas 5% of non-small-cell lung cancer (NSCLC) patients carry the inv(2)(p21;p23) rearrangement, encoding for the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion. /// Activity of second-generation ALK inhibitors against crizotinib-resistant mutants in an NPM-ALK model compared to EML4-ALK. /// Activity of second-generation ALK inhibitors against crizotinib-resistant mutants in an NPM-ALK model compared to EML4-ALK..
EML4_ALK- 23951022non small cell lung cancer;lung cancer FISH;PCR;RT-PCR - Recently Echinoderm microtubule-associated protein-like 4- anaplastic lymphoma kinase (EML4-ALK) fusion gene has become an important biomarker for ALK tyrosine kinase inhibitor (crizotinib) treatment in NSCLC. /// "Variants 3a+3b (4/5, 80%) of EML4-ALK fusion gene were more common to have high abundance of EML4-ALK positive cells in tumor tissues than variant 1 (1/3, 33.3%). " /// "Among the three detection methods, RT-PCR could detect not only the presence of EML4-ALK fusion gene and their variant types, but also the abundance of EML4-ALK positive cells in NSCLC tumor tissues. " /// "Variants 3a+3b (4/5, 80%) of EML4-ALK fusion gene were more common to have high abundance of EML4-ALK positive cells in tumor tissues than variant 1 (1/3, 33.3%)." /// "All of the 8 patients with high abundance of EML4-ALK positive cells in tumor tissues (assessed by the signal intensities of the RT-PCR product), were also have high expression of ALK protein (IHC3+), and positive for FISH, except one failed in FISH. " /// "All of the 8 patients with high abundance of EML4-ALK positive cells in tumor tissues (assessed by the signal intensities of the RT-PCR product), were also have high expression of ALK protein (IHC3+), and positive for FISH, except one failed in FISH." /// "However, the best detection method and the significance of EML4-ALK variant types remain uncertain. " /// "However, the best detection method and the significance of EML4-ALK variant types remain uncertain."
EML4_ALK- 20813423lung cancer PCR - We detected an EML4-ALK fusion gene using ELF in one patient. /// It has been reported that the existence of EGFR mutations and EML4-ALK gene rearrangements are related to the sensitivity of corresponding kinase inhibitors. /// We also examined EGFR mutations and EML4-ALK rearrangement.
EML4_ALK- 25806308lung cancer - - The discovery of the EML4-ALK fusion gene in a subgroup of patients with NSCLC and the subsequent clinical development of crizotinib has been an amazing success story in lung cancer translational-research, and its accelerated approval [only 4 years from the discovery of ALK rearrangement in NSCLC to the approval by the Food and Drug Administration (FDA)] marked the beginning of the new decade of targeted therapy.
EML4_ALK- 20926401non small cell lung cancer;lung cancer;adenocarcinoma PCR;ISH - EML4-ALK fusion gene assessment using metastatic lymph node samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration.. /// "Screening of these specimens with immunohistochemistry revealed ALK positivity in seven cases (6.4%), all of which possessed echinoderm microtubule-associated protein-like 4-ALK fusion genes as detected by fluorescent in situ hybridization and reverse transcription-PCR. "
EML4_ALK- 23341890non small cell lung cancer;lung cancer;adenocarcinoma - - Clinical significance of EML4-ALK fusion gene and association with EGFR and KRAS gene mutations in 208 Chinese patients with non-small cell lung cancer.. /// The EML4-ALK fusion gene has been recently identified in a small subset of non-small cell lung cancer (NSCLC) patients who respond positively to ALK inhibitors. /// "We identified 7 patients who harbored the EML4-ALK fusion gene (3.37%, 7/208), including 4 cases with variant 3 (57.1%), 2 with variant 1, and 1 with variant 2. " /// The characteristics of the EML4-ALK fusion gene in Chinese patients with NSCLC are poorly understood. /// "Taken together, EML4-ALK translocations were infrequent in the entire NSCLC patient population, but were frequent in the NSCLC subgroup of female, non-smoker, adenocarcinoma patients. " /// "The incidence of EML4-ALK translocation in female, non-smoking adenocarcinoma patients was as high as 15.2% (5/33). " /// "Meta-analysis demonstrated that EML4-ALK translocation occurred in 4.84% (125/2580) of unselected patients with NSCLC, and was also predominant in non-smoking patients with adenocarcinoma. " /// No EGFR/KRAS mutations were detected among the EML4-ALK positive patients. /// "Here, we report on the prevalence of EML4-ALK, EGFR status and KRAS mutations in 208 Chinese patients with NSCLC. "
EML4_ALK- 24982409non small cell lung cancer;lung cancer - - The responses to first-line cytotoxic chemotherapy were retrospectively compared between advanced or postoperative recurrent patients with non-squamous NSCLC who harbor the EML4-ALK fusion gene (ALK+), EGFR mutation (EGFR+), or neither abnormality (wild-type). /// Non-small cell lung cancer patients with EML4-ALK fusion gene are insensitive to cytotoxic chemotherapy.. /// NSCLC patients with the EML4-ALK fusion gene might be relatively insensitivite to cytotoxic chemotherapy.. /// "The responses to first-line cytotoxic chemotherapy were retrospectively compared between advanced or postoperative recurrent patients with non-squamous NSCLC who harbor the EML4-ALK fusion gene (ALK+), EGFR mutation (EGFR+), or neither abnormality (wild-type)." /// " Although patients with the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase gene (EML4-ALK) re-arrangement and epidermal growth factor gene EGFR mutations have proven sensitive to specific inhibitors, there is currently no consensus regarding the sensitivity of non-small cell lung cancer (NSCLC) patients with such mutations to cytotoxic chemotherapy. " /// "Although patients with the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase gene (EML4-ALK) re-arrangement and epidermal growth factor gene EGFR mutations have proven sensitive to specific inhibitors, there is currently no consensus regarding the sensitivity of non-small cell lung cancer (NSCLC) patients with such mutations to cytotoxic chemotherapy."
EML4_ALK- 25704901non small cell lung cancer;lung cancer - - These alterations have been defined as "driver mutations", such as mutations in EGFR and EML4-ALK fusion gene, and are highly sensitive to specific therapies. /// "Personalized medicine is now a reality for patients with advanced NSCLC on the basis of routine screening for EGFR, HER2, KRAS, BRAF, PI3KCA mutations and EML4-ALK rearrangement." /// "Personalized medicine is now a reality for patients with advanced NSCLC on the basis of routine screening for EGFR, HER2, KRAS, BRAF, PI3KCA mutations and EML4-ALK rearrangement. "
EML4_ALK- 23301645non small cell lung cancer;lung cancer - - EML4-ALK fusion gene, first described five years ago in patients with lung adenocarcinoma, undoubtedly has oncogenic potential and represents a promising candidate for targeted therapy. /// "[EML4-ALK fusion gene in patients with lung carcinoma: biology, diagnostics and targeted therapy].. " /// "Therefore, novel, highly specific inhibitors able to overcome resistance of mutated EML4-ALK are needed. " /// EML4-ALK fusion occurs due to paracentric inversion in the short arm of chromosome 2 and is detected in 3-5% of patients with non-small cell lung cancer.
EML4_ALK- 21475126non small cell lung cancer;lung cancer - - The EML4-ALK fusion gene was first identified as a potentially targetable oncogenic driver in non-small cell lung cancer in 2007. /// "Here we review the discovery of EML4-ALK, the development of clinical diagnostics for ALK rearrangements, the clinical epidemiology of lung cancers driven by EML4-ALK, and ongoing ALK inhibitor-based clinical trials.. " /// New targets in advanced NSCLC: EML4-ALK..
EML4_ALK- 18593892non small cell lung cancer;lung cancer - - The genome of a subset of non-small-cell lung cancers (NSCLC) harbors a small inversion within chromosome 2 that gives rise to a transforming fusion gene, EML4-ALK, which encodes an activated protein tyrosine kinase. /// "Although breakpoints within EML4 have been identified in introns 13 and 20, giving rise to variants 1 and 2, respectively, of EML4-ALK, it has remained unclear whether other isoforms of the fusion gene are present in NSCLC cells. " /// "Although breakpoints within EML4 have been identified in introns 13 and 20, giving rise to variants 1 and 2, respectively, of EML4-ALK, it has remained unclear whether other isoforms of the fusion gene are present in NSCLC cells." /// A lung cancer cell line expressing endogenous variant 3 of EML4-ALK underwent cell death on exposure to a specific inhibitor of ALK catalytic activity. /// Identification of novel isoforms of the EML4-ALK transforming gene in non-small cell lung cancer.. /// Both variants 3a and 3b of EML4-ALK exhibited marked transforming activity in vitro as well as oncogenic activity in vivo.
EML4_ALK- 25407901non small cell lung cancer;lung cancer PCR;RT-PCR - Interestingly, EML4-ALK fusion genes are more frequently found in younger patients and associated with less-differentiated carcinomas. /// "We have identified EML4-ALK fusion genes in 8 out of 95 carcinoma cases, accounting for 8.42% in Chinese male never-smokers with NSCLC." /// EML4-ALK fusion genes were detected using one-step real time RT-PCR and DNA sequencing. /// "Interestingly, EML4-ALK fusion genes are more frequently found in younger patients and associated with less-differentiated carcinomas. " /// "Thus, characterization of EML4-ALK fusion genes and clinical features of resulting carcinomas would be a great benefit to disease diagnosis and designing customized treatment plans. " /// "We have identified EML4-ALK fusion genes in 8 out of 95 carcinoma cases, accounting for 8.42% in Chinese male never-smokers with NSCLC. " /// Non-small cell lung cancer with EML4-ALK translocation in Chinese male never-smokers is characterized with early-onset. /// "In this study, we have determined the frequency of EML4-ALK translocation in male never-smokers with NSCLC in a cohort of Chinese patients." /// EML4-ALK translocation is associated with early-onset and less-differentiated carcinomas.. /// EML4-ALK translocation is associated with early-onset and less-differentiated carcinomas.. /// The clinical features associated with EML4-ALK translocation were also investigated. /// Non-small cell lung cancer with EML4-ALK translocation in Chinese male never-smokers is characterized with early-onset.. /// "In this study, we have determined the frequency of EML4-ALK translocation in male never-smokers with NSCLC in a cohort of Chinese patients. " /// The frequency of EML4-ALK translocation is strongly associated with smoking habits in Chinese male patients with higher frequency in male never-smokers. /// "Studies have suggested that EML4-ALK translocation occurs more frequently in never-smokers with NSCLC, especially in female patients. " /// "It has been suggested that EML4-ALK fusion is associated with the resistance in NSCLCs to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), such as gefitinib and erlotinib. "
EML4_ALK- 20624322non small cell lung cancer;lung cancer;adenocarcinoma PCR - The EML4-ALK fusion gene was present at a high frequency in Chinese NSCLC patients, particularly in those with adenocarcinomas lacking EGFR/KRAS mutations. /// "Within this cohort, the EML4-ALK fusion gene was identified in 12 tumors (11.6%). " /// "Further analysis revealed that EML4-ALK was present at a frequency of 16.13% (10/62) in patients with adenocarcinomas, 19.23% (10/52) in never-smokers, and 42.80% (9/21) in patients with adenocarcinomas lacking EGFR and KRAS mutations. " /// "The EML4-ALK fusion was associated with non-smokers (P = 0.03), younger age of onset (P = 0.03), and adenocarcinomas without EGFR/KRAS mutations (P = 0.04). " /// Concurrent deletion in EGFR exon 19 and fusion of EML4-ALK was identified for the first time in a Chinese female patient with an adenocarcinoma. /// "A trend towards improved survival was observed for patients with the EML4-ALK fusion, although it was not statistically significant (P = 0.20). " /// The EML4-ALK fusion appears to be tightly associated with ALK mRNA expression levels. /// "A trend towards improved survival was observed for patients with the EML4-ALK fusion, although it was not statistically significant (P = 0.20)."
EML4_ALK- 21753699non small cell lung cancer;lung cancer;adenocarcinoma - - A subset (1% to 5%) of non-small-cell lung carcinomas harbors the EML4-ALK fusion gene.
EML4_ALK- 23794492squamous cell carcinoma - - Lung adenocarcinoma (ADC) with the EML4-ALK fusion gene has been described as demonstrating mucinous cribriform/acinar growth and signet-ring cells, sometimes partially simulating SQCC.
EML4_ALK- 26710868non small cell lung cancer;lung cancer;adenocarcinoma PCR - The technique of fluorescent quantitative polymerase chain reaction (FQ-PCR) was employed for detecting the mutation rate of EGFR gene and EML4-ALK fusion gene for 40 cases of superficial lymph node tissue of NSCLC inpatients at General Military Hospital of Beijing PLA Command from February 2013 to November 2014. /// The mutation rate of EML4-ALK fusion gene was 2. /// The mutation rate of EGFR gene is high in adenocarcinoma and non-smokers while EML4-ALK fusion gene has a low mutation rate.. /// To explore the mutation status of epidermal growth factor receptor (EGFR) fusion gene and microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene in superficial lymph nodes of non-small cell lung cancer (NSCLC). /// [Mutations of EGFR gene and EML4-ALK fusion gene in superficial lymph node of non-small cell lung cancer]..
EML4_ALK- 22736493non small cell lung cancer;lung cancer;adenocarcinoma PCR;RT-PCR - EML4-ALK fusion genes have been recognized as novel "driver mutations" in a small subset of non-small cell lung cancers (NSCLC). /// "EML4-ALK fusion genes were identified by RT-PCR, whereas EGFR (Exons 18-21) and KRAS (Exons 1 and 2) mutations were detected by DNA sequencing. " /// Detection of EML4-ALK fusion genes in non-small cell lung cancer patients with clinical features associated with EGFR mutations.. /// Our data support the conclusion that the EML4-ALK fusion gene defines a new molecular subset of NSCLC with distinct pathologic features.. /// "Of the eight patients with EML4-ALK, none had an EGFR mutation, whereas a KRAS mutation was detected in one patient. " /// "Histologically, five of the EML4-ALK positive tumors were adenocarcinoma and two were mixed adenosquamous carcinoma. " /// "Thirty-one (31%) cases were wild type for EML4-ALK, EGFR, and KRAS mutations. " /// "Of the eight patients with EML4-ALK, none had an EGFR mutation, whereas a KRAS mutation was detected in one patient." /// The frequency of EML4-ALK fusions in NSCLC patients who have clinical characteristics related to EGFR mutation remains unknown. /// "Eight specimens (8%) were positive for EML4-ALK fusions, with seven being Variant 1 and one Variant 2. " /// "Eight specimens (8%) were positive for EML4-ALK fusions, with seven being Variant 1 and one Variant 2."
EML4_ALK- 22913857non small cell lung cancer;squamous cell carcinoma;lung cancer;adenocarcinoma - - Sixty-four fresh frozen tumor specimens were obtained from the tissue bank of Chang Gung Memorial Hospital for RNA extraction and EML4-ALK fusion gene detection. /// "In addition, NSCLC patients with the EML4-ALK fusion gene had a dramatic response and longer progression free survival after ALK inhibitor treatment than those without this fusion gene. " /// ALK overexpression detected by IHC study could be a promising detection method for the EML4-ALK fusion gene and is worth further confirmation with more samples.. /// Three of the 64 tumors (4.7%) had the EML4-ALK fusion gene. /// "Twenty patients with non-squamous cell carcinomas had epidermal growth factor receptor (EGFR) mutations, so the EML4-ALK fusion gene was found in 14.3% of EGFR wild type non-squamous cell carcinomas. " /// "When compared with other clinical and molecular features, only the IHC stain for ALK was significantly correlated with the EML4-ALK fusion gene (p = 0.0002). " /// Recently the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene with transforming activity was identified in non-small cell lung cancer (NSCLC). /// "However, the incidence and clinical and molecular characteristics of the EML4-ALK fusion gene in NSCLC patients of Taiwan are still unclear. " /// Correlation of anaplastic lymphoma kinase overexpression and the EML4-ALK fusion gene in non-small cell lung cancer by immunohistochemical study..
EML4_ALK- 20183914non small cell lung cancer PCR;RT-PCR - We screened for EML4-ALK fusion genes and examined the clinicopathological and genetic characteristics of fusion-harboring NSCLC tumors. /// Clinicopathologic features of non-small-cell lung cancer with EML4-ALK fusion gene.. /// Five EML4-ALK fusion genes were detected (four from 111 female samples and one from 202 male samples. /// "EML4-ALK fusion genes were observed predominantly in adenocarcinomas, in female or nonsmoking populations. " /// "Additionally, the EML4-ALK fusions were mutually exclusive with mutations in the EGFR, KRAS, and ERBB2 genes.. "
EML4_ALK- 21719143adenocarcinoma PCR;RT-PCR - We herein report a case of signet ring cell adenocarcinoma of the lung with an EML4-ALK fusion gene mimicking mucinous (colloid) adenocarcinoma. /// Signet ring cell adenocarcinoma of the lung with an EML4-ALK fusion gene mimicking mucinous (colloid) adenocarcinoma: a case report.. /// "The postoperative pathological examination revealed signet ring cell carcinoma with abundant mucin pools, and a multiplex RT-PCR analysis revealed the variant 2 inversion of the EML4-ALK gene.. " /// "The postoperative pathological examination revealed signet ring cell carcinoma with abundant mucin pools, and a multiplex RT-PCR analysis revealed the variant 2 inversion of the EML4-ALK gene.."
EML4_ALK- 22494566non small cell lung cancer;lung cancer;adenocarcinoma PCR;RT-PCR - A total of 161 cell samples, from cases without available tissue samples, obtained by bronchoscopic examinations utilized for immediate cytology in patients with NSCLC were subsequently analyzed for EML4-ALK fusion genes using a nested multiplex RT-PCR. /// The efficacy of RT-PCR for detection of EML4-ALK fusion genes in transbronchial cytological specimens has not been studied. /// The RNA was extracted and the sensitivity of detection of the EML4-ALK fusion gene was determined using a nested RT-PCR. /// "Here, we evaluated the detection rate of EML4-ALK fusion genes in transbronchial cytological specimens positive for NSCLC by immediate cytology during bronchoscopic examination. " /// "In the patient cytological samples, EML4-ALK fusion genes were detected in five of 161 NSCLCs (3.1%) and four of 88 adenocarcinomas (4.5%). " /// "A total of 161 cell samples, from cases without available tissue samples, obtained by bronchoscopic examinations utilized for immediate cytology in patients with NSCLC were subsequently analyzed for EML4-ALK fusion genes using a nested multiplex RT-PCR. " /// EML4-ALK fusion genes as well as EGFR mutations were successfully detected in a small number of cancer cells from transbronchial cytological specimens using a nested multiplex RT-PCR. /// Detection of EML4-ALK fusion genes in a few cancer cells from transbronchial cytological specimens utilizing immediate cytology during bronchoscopy.. /// There was no case in which both EML4-ALK fusion and EGFR mutation were simultaneously detected. /// Various numbers of H2228 cells carrying EML4-ALK variant 3 were combined with 1??10(6) wild-type WBCs. /// "EML4-ALK variant 3 was detected in a small number of H2228 cells (10 cells), even in the presence of 1??10(6) WBCs (sensitivity: 0.001%). "
EML4_ALK- 23714228non small cell lung cancer;lung cancer - - The EML4-ALK fusion gene occurs generally in NSCLC without mutations in epidermal growth factor receptor (EGFR) and KRAS. /// The EML4-ALK (echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene) fusion oncogene represents a novel molecular target in a small subset of non-small-cell lung cancers (NSCLCs).
EML4_ALK- 21168933non small cell lung cancer;lung cancer - - The fusion gene EML4-ALK (echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene) was recently identified as a novel genetic alteration in non-small cell lung cancer (NSCLC). /// "EML4-ALK translocations correlate with specific clinical and pathological features, in particular lack of EGFR and K-ras mutations, and may be associated with resistance to EGFR tyrosine-kinase inhibitors (TKIs). " /// EGFR and EML4-ALK gene mutations in NSCLC: a case report of erlotinib-resistant patient with both concomitant mutations..
EML4_ALK- 23731739adenocarcinoma - - A case of lung adenocarcinoma harboring exon 19 EGFR deletion and EML4-ALK fusion gene.. /// We report a man with advanced adenocarcinoma who harboring exon 19 (E746-A750del) epidermal growth factor receptor (EGFR) deletion and echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) gene translocation in the re-biospy specimen.
EML4_ALKinv (2)(p21p23) / 19064915lung cancer;adenocarcinoma - - EML4-ALK is a fusion-type protein tyrosine kinase that is generated in human non-small-cell lung cancer (NSCLC) as a result of a recurrent chromosome inversion, inv (2)(p21p23). /// "injection of 3T3 cells expressing EML4-ALK induced lethal respiratory failure in recipient nude mice, administration of the ALK inhibitor effectively cleared the tumor burden and improved the survival of such animals. " /// "These data together reinforce the pivotal role of EML4-ALK in the pathogenesis of NSCLC in humans, and they provide experimental support for the treatment of this intractable cancer with ALK inhibitors.. " /// "To address this issue, we have now established transgenic mouse lines that express EML4-ALK specifically in lung alveolar epithelial cells. " /// "To address this issue, we have now established transgenic mouse lines that express EML4-ALK specifically in lung alveolar epithelial cells."
EML4_ALK- 21102267- - - Good response to gefitinib in lung adenocarcinoma harboring coexisting EML4-ALK fusion gene and EGFR mutation..
EML4_ALK- 24388371non small cell lung cancer;squamous cell carcinoma;lung cancer;adenocarcinoma - - A specific ALK inhibitor has been shown to exert anti-tumor effects in NSCLC with the EML4-ALK fusion gene. /// The tumor specimens were examined by immunohistochemistry for the EML4-ALK fusion gene and by polymerase chain reaction for epidermal growth factor receptor (EGFR) mutations. /// The EML4-ALK fusion gene was further detected in 2 cases of undifferentiated cell carcinoma. /// "EML4-ALK fusion gene examinations could be more effectively performed by selecting young NSCLC patients without EGFR mutations, whereas selection on the basis of a non-smoking or adenocarcinoma history, as reported in previous studies, may not correctly identify the patient groups with potential EML4-ALK fusion gene.. " /// Effective enrichment strategy for EML4-ALK fusion gene screening in patients with non-small cell lung cancer.. /// "Between January 2004 and September 2011, the EML4-ALK fusion gene was detected in 19.6% (9/46) of patients. " /// "Previous reports suggested an EML4-ALK incidence of approximately 5% in a pan-NSCLC population, with an increased frequency in younger patients, but an appropriate strategy for further selecting patients with the EML4-ALK fusion gene remains unknown. "
EML4_ALK- 26767009non small cell lung cancer;lung cancer - - Patients with the EML4-ALK fusion gene were significantly younger (P< 0.001). /// The optimal time lag from the obtainment of the pathological tissue to the time of EML4-ALK fusion gene detection is ?48 months.. /// The detection rate of the EML4-ALK fusion gene in patients who received primary tumor or metastatic lymph node resection was significantly higher than in patients who received fine-needle biopsy (P= 0.003). /// The echinoderm microtubule-associated protein-like-4-anaplastic lymphoma kinase (EML4-ALK) fusion gene defines a novel molecular subset of non-small-cell lung cancer (NSCLC). /// "However, the clinicopathological features of patients with the EML4-ALK fusion gene have not been defined completely. " /// "The EML4-ALK fusion gene was detected in 56 (28.0%) of the 200 NSCLC patients, and undetected in 22 (11.0%) patients because of an insufficient amount of pathological tissue. " /// Younger age and wild-type EGFR were identified as clinicopathological characteristics of patients with advanced NSCLC who harbored the EML4-ALK fusion gene. /// The occurrence of the EML4-ALK fusion gene in patients with wild-type epidermal growth factor receptor (EGFR) was significantly higher than in patients with mutant-type EGFR (42.5% [37/87] vs. /// The detection rate of the EML4-ALK fusion gene in patients with a time lag from obtainment of the pathological tissue to EML4-ALK fusion gene detection ?48 months was significantly higher than in patients >48 months (P= 0.020). /// Clinicopathological data of 200 Chinese patients with advanced NSCLC were analyzed retrospectively to explore their possible correlations with EML4-ALK fusions. /// "The median age of the patients with positive and negative EML4-ALK was 48 and 55 years, respectively. "
EML4_ALK- 22989458non small cell lung cancer;lung cancer;adenocarcinoma - - Moreover, in 2007 the existence of the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene was discovered in NSCLC, and the same as EGFR-TKIs, ALK inhibitors are being found to be highly effective in lung cancers. /// "Moreover, in 2007 the existence of the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene was discovered in NSCLC, and the same as EGFR-TKIs, ALK inhibitors are being found to be highly effective in lung cancers. "
EML4_ALK- 23787064small cell lung cancer - - However, the presence of an EML4-ALK fusion gene in other lung cancer histologies is an extremely rare phenomenon. /// An extremely rare case of small-cell lung cancer harboring variant 2 of the EML4-ALK fusion gene.. /// "Surprisingly, the tumor was genetically considered to harbor the EML4-ALK fusion gene (variant 2). " /// "However, the presence of an EML4-ALK fusion gene in other lung cancer histologies is an extremely rare phenomenon." /// "Our analysis of 30 consecutive patients with SCLC for EML4-ALK revealed that two patients, including the current patient and a patient we previously reported, harbored the EML4-ALK fusion gene. " /// "Our analysis of 30 consecutive patients with SCLC for EML4-ALK revealed that two patients, including the current patient and a patient we previously reported, harbored the EML4-ALK fusion gene."
EML4_ALK- 23609245non small cell lung cancer;lung cancer - - EGFR mutations and EML4-ALK fusion gene could be evaluated in all patients with non-small cell lung cancer (n=20) using EUS-B-FNA samples. /// Epidermal growth factor receptor (EGFR) mutations and echinoderm microtubule-associated protein-like 4 and the anaplastic lymphoma kinase (EML4-ALK) fusion gene were evaluated using EUS-B-FNA samples of non-small cell lung cancer.
EML4_ALK- 21245935non small cell lung cancer;lung cancer - - The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene resulting from an inversion within chromosome 2p occurs in approximately 5% of non-small cell lung cancer and is mutually exclusive with Ras and EGFR mutations. /// The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene resulting from an inversion within chromosome 2p occurs in approximately 5% of non-small cell lung cancer and is mutually exclusive with Ras and EGFR mutations. /// "We show here that TAE684 inhibits proliferation and induces cell cycle arrest, apoptosis, and tumor regression in two NSCLC models that harbor EML4-ALK fusions." /// "We also compared the effect of TAE684 with PF2341066, a c-Met and ALK small molecule inhibitor currently in clinical trial in cancers harboring ALK fusions, and demonstrated that TAE684 is a much more potent inhibitor of EML4-ALK. " /// "In this study, we have used a potent and selective ALK small molecule inhibitor, NPV-TAE684, to assess the oncogenic role of EML4-ALK in non-small cell lung cancer (NSCLC). " /// We used microarray analysis to carry out targeted pathway studies of gene expression changes in H2228 NSCLC xenograft model after TAE684 treatment and identified a gene signature of EML4-ALK inhibition. /// "TAE684 inhibits EML4-ALK activation and its downstream signaling including ERK, AKT, and STAT3. " /// Our data demonstrate that EML4-ALK plays an important role in the pathogenesis of a subset of NSCLC and provides insight into the mechanism of EML4-ALK inhibition by a small molecule inhibitor.. /// "We show here that TAE684 inhibits proliferation and induces cell cycle arrest, apoptosis, and tumor regression in two NSCLC models that harbor EML4-ALK fusions. " /// Evaluation of EML4-ALK fusion proteins in non-small cell lung cancer using small molecule inhibitors..
EML4_ALK- 23181703non small cell lung cancer;lung cancer;adenocarcinoma - - We report a 39-year-old patient diagnosed as adenocarcinoma harboring EGFR mutation and EML4-ALK fusion gene. /// A case of lung adenocarcinoma harboring EGFR mutation and EML4-ALK fusion gene.. /// We experienced a rare case with EGFR mutation and EML4-ALK. /// Patients who harbor EML4-ALK fusions have been associated with a lack of EGFR or KRAS mutations.
EML4_ALK- 18594010non small cell lung cancer;lung cancer;adenocarcinoma PCR - EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer.. /// The EML4-ALK fusion gene has been detected in approximately 7% of Japanese non-small cell lung cancers (NSCLC). /// "We detected four different variants, including two novel variants, of EML4-ALK using reverse transcription-PCR in 8 of 305 tumors (3%) and 3 of 83 (3.6%) NSCLC cell lines. " /// We determined the frequency of EML4-ALK in Caucasian NSCLC and in NSCLC cell lines. /// EML4-ALK was detected more frequently in NSCLC patients who were never or light (<10 pack-years) cigarette smokers compared with current/former smokers (6% versus 1%. /// "In another EML4-ALK cell line, DFCI032, TAE684 was ineffective due to coactivation of epidermal growth factor receptor and ERBB2. " /// EML4-ALK is found in the minority of NSCLC. /// ALK kinase inhibitors alone or in combination may nevertheless be clinically effective treatments for NSCLC patients whose tumors contain EML4-ALK.. /// EML4-ALK was detected more frequently in NSCLC patients who were never or light (<10 pack-years) cigarette smokers compared with current/former smokers (6% versus 1%; P = 0.049).
EML4_ALK- 25676402T cell lymphoma - - But the report that malignant lymphoma complicated with lung adenocarcinoma harboring EML4-ALK fusion gene in one individual is rare. /// Echinoderm microtubule associated protein like 4 anaplastic lymphoma kinase (EML4-ALK) as a new biological marker is a hot topic in the field of lung cancer treatment. /// [A case report: an EML4-ALK positive lung adenocarcinoma diagnosed ?with lymphoma previously].. /// "Here, we report an EML4-ALK positive non-small cell lung cancer (NSCLC) in a patient previously diagnosed with T cell lymphoma and review literature on metachronous lung cancer complicating with lymphoma. "
EML4_ALK- 24156959non small cell lung cancer;lung cancer - - The discovery of EML4-ALK fusion gene in a subgroup of patients with lung adenocarcinoma led to the development of a new class of agents, the ALK inhibitors, and dramatically improved the clinical outcome of these patients. /// "In the current review, we will analyze the biology of EML4-ALK gene, the acquired resistance mechanisms to crizotinib, the therapeutic strategies, currently under evaluation, designed to overcome crizotinib resistance, and the open issues that need to be addressed in order to improve outcome in ALK+ Non Small Cell Lung Cancer (NSCLC) patients." /// "In the current review, we will analyze the biology of EML4-ALK gene, the acquired resistance mechanisms to crizotinib, the therapeutic strategies, currently under evaluation, designed to overcome crizotinib resistance, and the open issues that need to be addressed in order to improve outcome in ALK+ Non Small Cell Lung Cancer (NSCLC) patients. "
EML4_ALK- 22323876non small cell lung cancer;lung cancer;adenocarcinoma - - EML4-ALK fusion genes have been detected in 10 (6.0%) of 167 patients of NSCLCs and in 9 (7.4%) of 121 patients of adenocarcinoma. /// EML4-ALK fusion gene in Korean non-small cell lung cancer.. /// "Although a few studies have evaluated EML4-ALK fusion genes in Korean NSCLCs, the prevalence of different EML4-ALK fusion variants has yet to be clearly assessed. " /// These results indicate that the profiles of EML4-ALK fusion gene variants in Korean patients of NSCLC may differ from those in other ethnic populations. /// "Herein, we have examined the profiles of EML4-ALK fusion gene variants in Korean patients of NSCLCs. " /// "Herein, we describe for the first time the profiles of EML4-ALK fusion variants of Korean patients with NSCLCs.. "
EML4_ALK- 23769348non small cell lung cancer;lung cancer - - After epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs), crizotinib targeted at EML4-ALK fusion gene becomes a significant drug of molecular targeted therapy in NSCLC. /// "After epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs), crizotinib targeted at EML4-ALK fusion gene becomes a significant drug of molecular targeted therapy in NSCLC. " /// "Phase I and II clinical trials prove that crizotinib is effective for treatment of activating EML4-ALK mutation in advanced NSCLC patients, little side-effect, and well tolerated. "
EML4_ALK- 20659620non small cell lung cancer;lung cancer;adenocarcinoma - - The fusion gene EML4-ALK (echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene) was recently identified as a novel genetic alteration in non-small-cell lung cancer.
EML4_ALK- 19234440lung cancer;adenocarcinoma - - A subset of lung cancers harbors a small inversion within chromosome 2p, giving rise to a transforming fusion gene, EML4-ALK (echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene), which encodes an activated tyrosine kinase. /// " A subset of lung cancers harbors a small inversion within chromosome 2p, giving rise to a transforming fusion gene, EML4-ALK (echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene), which encodes an activated tyrosine kinase. " /// "We have earlier examined the presence of EML4-ALK by multiplex reverse transcription-polymerase chain reaction in 363 specimens of lung cancer, identifying 11 adenocarcinoma cases featuring the fusion gene. " /// "EML4-ALK lung cancers are characterized by rare other mutations, a TTF-1 cell lineage, an acinar histology, and young onset." /// "EML4-ALK lung cancers are characterized by rare other mutations, a TTF-1 cell lineage, an acinar histology, and young onset.. " /// "Furthermore, the presence of EML4-ALK appears to be mutually exclusive for EGFR and KRAS mutations (P=0.00018), whereas coexisting with TP53 mutations at a low frequency (1/11=9.1%), and correlating with non- or light smoking (P=0.040), in line with the TTF-1 immunoreactivity. "
EML4_ALK- 24419120- - - Long-term response to gefitinib and crizotinib in lung adenocarcinoma harboring both epidermal growth factor receptor mutation and EML4-ALK fusion gene..
EML4_ALK- 21102268lung cancer - - Treatment of lung cancer with an ALK inhibitor after EML4-ALK fusion gene detection using endobronchial ultrasound-guided transbronchial needle aspiration..
EML4_ALK- 26019170non small cell lung cancer;lung cancer PCR - We have now examined PD-L1 expression and its regulation in NSCLC positive for the EML4-ALK fusion gene. /// We have now examined PD-L1 expression and its regulation in NSCLC positive for the EML4-ALK fusion gene. /// The PD-L1 expression level was higher in NSCLC cell lines positive for EML4-ALK than in those negative for the fusion gene. /// "Finally, the expression level of PD-L1 was positively associated with the presence of EML4-ALK in NSCLC specimens." /// "Finally, the expression level of PD-L1 was positively associated with the presence of EML4-ALK in NSCLC specimens. " /// "Furthermore, expression of PD-L1 was downregulated by inhibitors of the MEK-ERK and PI3K-AKT signaling pathways in NSCLC cells positive for either EML4-ALK or activating mutations of the EGFR. " /// Our findings that both EML4-ALK and mutant EGFR upregulate PD-L1 by activating PI3K-AKT and MEK-ERK signaling pathways in NSCLC reveal a direct link between oncogenic drivers and PD-L1 expression.. /// Induction of PD-L1 Expression by the EML4-ALK Oncoprotein and Downstream Signaling Pathways in Non-Small Cell Lung Cancer..
EML4_ALK- 23371030non small cell lung cancer;lung cancer - - For instance, several molecular alterations have been defined as "driver mutations," such as mutations in EGFR and EML4-ALK fusion gene. /// "For instance, several molecular alterations have been defined as ""driver mutations,"" such as mutations in EGFR and EML4-ALK fusion gene. "
EML4_ALK- 23425902non small cell lung cancer;lung cancer - - In recent years, more and more attention has been focused on some new molecular targets in NSCLC, such as echinodem microtubule-associated protein-like4/anaplastic lymphoma kinase (EML4-ALK) fusion gene. /// [Clinical meaning of EML4-ALK fusion gene in non-small cell lung cancer].. /// "In recent years, more and more attention has been focused on some new molecular targets in NSCLC, such as echinodem microtubule-associated protein-like4/anaplastic lymphoma kinase (EML4-ALK) fusion gene. " /// "This review will focus on the basic structure, clinicopathologic features, detection method, ALK inhibitor and therapeutic meaning of EML4-ALK in NSCLC.. "
EML4_ALK- 22154278non small cell lung cancer - - For instance, several molecular alterations have been defined as "driver mutations," such as mutations in epidermal growth factor receptor (EGFR), Kirsten-rous avian sarcoma (KRAS), and a chromosome 2p inversion producing an EML4-ALK fusion gene (echinoderm microtubule-associated protein-like 4 fused with the anaplastic lymphoma kinase). /// "For instance, several molecular alterations have been defined as ""driver mutations,"" such as mutations in epidermal growth factor receptor (EGFR), Kirsten-rous avian sarcoma (KRAS), and a chromosome 2p inversion producing an EML4-ALK fusion gene (echinoderm microtubule-associated protein-like 4 fused with the anaplastic lymphoma kinase). "
EML4_ALK- 21504625non small cell lung cancer;breast cancer;lung cancer;ovarian cancer - - EML4-ALK fusion gene is identified in approximately 3-13% of non-small cell lung cancer (NSCLC). /// "Early-phase clinical studies with Crizotinib, an ALK inhibitor, in NSCLC harboring EML4-ALK have demonstrated promising activity with high response rate and prolonged progression-free survival. "
EML4_ALK- 22868512non small cell lung cancer;lung cancer - - Furthermore, the article summarizes the implications and future prospects of using molecular testing in the field of NSCLC with focus on EGFR mutations, KRAS mutation, EML4-ALK fusion gene detection, and EGFR expression.. /// This article discusses in detail the significance of first-line and second-line epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and inhibitors of the vascular endothelial growth factor receptor (VEGFR) and EML4-ALK.
EML4_ALK- 21515061non small cell lung cancer;lung cancer - - Since the identification of the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene in some NSCLC patients was reported in 2007, various research groups have been seeking ALK inhibitors.
EML4_ALK- 26719536non small cell lung cancer - - One cell line lost the EML4-ALK fusion gene, but exhibited increased activation of insulin-like growth factor-1 receptor (IGF1R) and human epidermal growth factor receptor 3 (HER3), and overexpressed the HER3 ligand neuregulin 1.
EML4_ALK- 21129606adenocarcinoma - - Up till now EGFR gene mutations, KRAS gene mutations and EML4-ALK fusion genes are the most widely recognized alterations involved in both the biology and the clinical management of lung adenocarcinoma.
EML4_ALK- 22336240lung cancer - - [EML4-ALK fusion gene in lung cancer and its biological function]..
EML4_ALK- 27070423lung cancer;lung cancer - - Patients should be screened for the presence of the EGFR mutation or echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene prior to chemotherapy to predict their clinical response. /// "HCC827 (Exon19: E746-A750 del) and H3122 (EML4-ALK) cells were inhibited by lower concentrations of erlotinib and crizotinib, respectively than A549, H460, and H1975 (L858R+T790M) cells were. "
EML4_ALK- 25941796lung cancer;lung cancer - - In addition, we discuss potential future treatment strategies in ALK-TKI-na?ve and -resistant patients with lung cancer harboring the EML4-ALK fusion gene.
EML4_ALK- 26644092lung cancer;lung cancer - - the most famous and useful of them the fusion gene ALK-EML4 but other oncogenic pathways have been implicated and under investigations including HER2, BRAF, MET, RET...
EML4_ALK- 24755712lung cancer - - The EML4-ALK fusion gene is more frequently found in younger, never smoking patients with lung cancer. /// "We, therefore, hypothesized that SHS, which can induce DNA damage, is associated with the EML4-ALK fusion gene. " /// We compared the frequency of the EML4-ALK fusion gene among 197 never smoker patients with lung cancer with and without a history of exposure to SHS during childhood at Mayo Clinic. /// The EML4-ALK fusion gene is not enriched in tumors from individuals exposed to SHS during childhood. /// Evidence that the lung Adenocarcinoma EML4-ALK fusion gene is not caused by exposure to secondhand tobacco smoke during childhood.. /// "The EML4-ALK fusion gene was detected in 33% of cases from never smokers with a history of SHS exposure during childhood, whereas 47% of never smoking lung cancer cases without a history of childhood SHS exposure tested positive for the fusion gene. " /// These data suggest that childhood exposure to SHS is not a significant etiologic cause of the EML4-ALK fusion gene in lung cancer..
EML4_ALK- 22336170non small cell lung cancer;lung cancer - - [Study of EML4-ALK fusion gene as a biomarker in non-small cell lung cancer]..
EML4_ALK- 25180059- - - Among the 50 EGFR wild type patients who detected fusion genes, 14 carried EML4-ALK fusion (28%), 2 had TPM3-ROS1 fusion (4%), and 3 harbored KIF5B-RET fusion (6%).
EML4_ALK- 24277751lung cancer;sarcoma - - Pulmonary inflammatory myofibroblastic tumor harboring EML4-ALK fusion gene..
EML4_ALK- 27103824non small cell lung cancer;lung cancer - - We aimed at revealing the clinical features of EML4-ALK fusion gene and EGFR mutation in non-small-cell lung cancer (NSCLC). /// The EGFR mutations and the EML4-ALK fusion genes are coexistent.. /// Six patients who harbored both EML4-ALK fusion genes and EGFR mutations were identified in our study. /// EML4-ALK fusion gene defines a new molecular subset in patients with NSCLC. /// "In continuity correction ?? (2) test analysis, EML4-ALK fusion gene was correlated with sex, age, smoking status, and histology, but no significant association was observed between EML4-ALK fusion gene and clinical stage. " /// "EML4-ALK fusion gene was analyzed by real-time polymerase chain reaction, and EGFR mutations were analyzed by amplified refractory mutation system. " /// Detection of EML4-ALK fusion gene and features associated with EGFR mutations in Chinese patients with non-small-cell lung cancer.. /// Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) and epidermal growth factor receptor (EGFR) define specific molecular subsets of lung cancer with distinct clinical features. /// "Among the 694 patients, 60 (8.65%) patients had EML4-ALK fusions. " /// "Meanwhile, to our surprise, six (0.86%) patients had coexisting EML4-ALK fusions and EGFR mutations. "
EML4_ALK- 21569650- - - [The EML4-ALK fusion gene in NSCLC and the clinical progress]..
EML4_ALK- 25806349solitary pulmonary nodule - - The patient took a second operation "the right middle lobe resection" and was diagnosed as left lung adenocarcinoma at TNM stage IV (pT3N2M1a, two lungs) with neither EGFR mutation nor ALK-EML4 fusion gene.
EML4_ALK- 22980554lung cancer;adenocarcinoma - - EML4-ALK fusion gene, is found in 3 to 5 % of lung adenocarcinoma and can be targeted by tyrosine-kinase inhibitor (TKI) with impressive therapeutic results.
EML4_ALK- 22563229leukemia;lung cancer - - Detection of EML4-ALK and other ALK fusion genes in lung cancer: a lesson from the leukemia fusion gene analysis and future application..
EML4_ALK- 22104224non small cell lung cancer;lung cancer - - However, cases of patients harbored concomitant EML4-ALK fusion gene and EGFR mutation have been reported continuously at recent. /// [Research progress in non-small cell lung cancer with concomitant EML4-ALK fusion gene and EGFR gene mutation].. /// "This review aims to summarize the incidence and molecular structure of EML4-ALK fusion gene and EGFR mutation, as well as clinical features of patients with the concomitant genes induced NSCLC.. " /// "Molecular target therapy is one of the most popular and promising field of NSCLC treatment, and its hotspots includes EGFR (epidermal growth factor receptor), EML4-ALK (echinoderm microtubule associated protein like4-anaplastic lymphoma kinase), etc. " /// Former researches indicated that EML4-ALK fusion and EGFR mutation were excluded mutually.
EML4_ALK- 25360721non small cell lung cancer;lung cancer;adenocarcinoma - - Clinicopathologic features of patients with non-small cell lung cancer harboring the EML4-ALK fusion gene: a meta-analysis.. /// "A significant lower EML4-ALK fusion gene positive rate was associated with smokers (pooled OR?=?0.40, 95% CI?=?0.30-0.54, P<0.00001). " /// "The frequency of the EML4-ALK fusion gene and the clinicopathologic features, including smoking status, pathologic type, gender, and EGFR status were abstracted. " /// This meta-analysis was conducted to compare the frequency of the EML4-ALK fusion gene in patients with different clinicopathologic features and to identify an enriched population of patients with NSCLC harboring EML4-ALK fusion gene. /// The Pubmed and Embase databases for all studies on EML4-ALK fusion gene in NSCLC patients were searched up to July 2014. /// The key demographic and pathologic features associated with EML4-ALK fusion gene have not been definitively established. /// The frequencies of EML4-ALK fusion gene in non-small cell lung cancer (NSCLC) with different clinicopathologic features described by previous studies are inconsistent. /// "We found that a significantly lower EML4-ALK fusion gene positivity rate was associated with EGFR mutation (pooled OR?=?0.07, 95% CI?=?0.03-0.19, P<0.00001). " /// "This meta-analysis revealed that the EML4-ALK fusion gene is highly correlated with a never/light smoking history, female and the pathologic type of adenocarcinoma, and is largely mutually exclusive of EGFR.. " /// "A significantly higher EML4-ALK fusion gene positivity rate was associated with adenocarcinomas (pooled OR?=?2.53, 95% CI?=?1.66-3.86, P<0.0001) and female (pooled OR?=?0.61, 95% CI?=?0.41-0.90, P?=?0.01). "
EML4_ALK- 23936355non small cell lung cancer;lung cancer;adenocarcinoma FISH;PCR;RT-PCR - EML4-ALK fusion gene is found in only a small subset (2-6%) of non-small cell lung cancer.
EML4_ALKinv(2)(p21p23) / 19032370prostate cancer;non small cell lung cancer;lung cancer - - Non-solid oncogenes in solid tumors: EML4-ALK fusion genes in lung cancer.. /// "In the present review I summarize how detection of EML4-ALK cDNA may become a sensitive diagnostic means for NSCLC cases that are positive for the fusion gene, and discuss whether suppression of ALK enzymatic activity could be an effective treatment strategy against this intractable disorder.. " /// "Break and fusion points within the EML4 locus may diverge in NSCLC cells to generate various isoforms of EML4-ALK, which may constitute approximately 5% of NSCLC cases, at least in the Asian ethnic group. " /// "EML4-ALK oligomerizes constitutively in cells through the coiled coil domain within the EML4 region, and becomes activated to exert a marked oncogenicity both in vitro and in vivo. "
EML4_ALK- 24504521prostate cancer PCR - The identification of recurrent gene fusions in common epithelial cancers--for example, TMPRSS2/ERG in prostate cancer and EML4/ALK in nonsmall cell lung carcinomas--has raised the question of whether fusion genes are pathogenetically important also in ovarian carcinomas. /// " The identification of recurrent gene fusions in common epithelial cancers--for example, TMPRSS2/ERG in prostate cancer and EML4/ALK in nonsmall cell lung carcinomas--has raised the question of whether fusion genes are pathogenetically important also in ovarian carcinomas. "
EML4_ALK- 17625570non small cell lung cancer;lung cancer - - Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.. /// The EML4-ALK fusion transcript was detected in 6.7% (5 out of 75) of NSCLC patients examined.
EML4_ALK- 27066085non small cell lung cancer;squamous cell carcinoma;lung cancer - - RNA-seq data identified oncogenic fusion genes EML4-ALK and SLC34A2-ROS1 in three of 86 normal-cancer paired samples.
EML4_ALK- 20483705chronic myeloid leukemia;myeloid leukemia;leukemia;lung cancer - - The fusion proteins from the ALK gene have been identified in oncohaematology malignancies including ALK positive anaplastic lymphoma large cell and non small cells lung cancer with EML4-ALK fusion gene.
EML4_ALK- 25695223pleural effusion - - Analysis of ERBB ligand-induced resistance mechanism to crizotinib by primary culture of lung adenocarcinoma with EML4-ALK fusion gene..
EML4_ALK10p11.22 / 22797671papillary adenocarcinoma PCR;RT-PCR - The fusion genes were detected exclusively with other mutations, such as EGFR, Kras, Braf, erbB2 mutations, and EML4/ALK fusion. /// The cinicopathological backgrounds of the KIF5B/RET fusion-positive patients were similar with those of the EML4/ALK fusion-positive patients.
EML4_ALK- 24935562adenocarcinoma - - We also identified 8 patients who harbored the EML4-ALK fusion gene (8.7%, 8/92). /// The serum CEA level before the initial treatment may be helpful in screening population for EGFR mutations or EML4-ALK fusion gene presence in lung adenocarcinoma patients.. /// Our purpose was to analyze clinical features and prognostic value of EGFR gene mutations and the EML4-ALK fusion gene in lung adenocarcinoma. /// "In addition, the frequency of the EML4-ALK fusion gene among patients with a serum CEA concentration below 5 ng/ml seemed to be higher than patients with a concentration over 5 ng/ml (P=0.021). " /// EGFR gene mutations and the EML4-ALK fusion gene were detected in 92 lung adenocarcinoma patients in China. /// "We also identified 8 patients who harbored the EML4-ALK fusion gene (8.7%, 8/92). " /// Serum carcinoembryonic antigen levels before initial treatment are associated with EGFR mutations and EML4- ALK fusion gene in lung adenocarcinoma patients.. /// Epidermal growth factor receptor (EGFR) mutations and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) define specific molecular subsets of lung adenocarcinomas with distinct clinical features. /// Epidermal growth factor receptor (EGFR) mutations and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) define specific molecular subsets of lung adenocarcinomas with distinct clinical features.
EML4_ALK- 22986231non small cell lung cancer;lung cancer - - The EML4-ALK fusion gene encodes a chimeric tyrosine kinase that activates the Ras signaling pathway, and this fusion protein is found in approximately 5% of NSCLC. /// We present the clinicopathologic features of three patients with metastatic NSCLC harboring the EML4-ALK translocation that developed isolated central nervous system (CNS) metastases in the presence of good disease control elsewhere in the body. /// "While understanding molecular mechanisms of resistance is critical to overcome therapeutic resistance, understanding physiologic mechanisms of resistance through analyzing anatomic patterns of failure may be equally crucial to improve long-term survival for patients with EML4-ALK translocation positive NSCLC.. " /// Isolated central nervous system progression on Crizotinib: an Achilles heel of non-small cell lung cancer with EML4-ALK translocation?. /// "Targeting EML4-ALK with Crizotinib in this subset of NSCLC has documented therapeutic efficacy, but the vast majority of patients eventually develop recurrent disease that is often refractory to further treatments." /// Results of ongoing clinical trials will clarify whether the CNS is a major sanctuary site for EML4-ALK positive NSCLC being treated with Crizotinib. /// "Targeting EML4-ALK with Crizotinib in this subset of NSCLC has documented therapeutic efficacy, but the vast majority of patients eventually develop recurrent disease that is often refractory to further treatments. "
EML4_ALK- 23708071non small cell lung cancer;lung cancer - - The EML4-ALK fusion gene appears unique to lung cancer and signals through extracellular signal regulated kinase and phosphoinositide 3-kinase. /// "Membrane phospholipids, EML4-ALK, and Hsp90 as novel targets in lung cancer treatment.. " /// The echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) is member of the insulin superfamily of receptor tyrosine kinases. /// "In this review we focus on radiosensitizing strategies involving the targeting of membrane phospholipids, EML4-ALK, and Hsp90 with specific inhibitors and briefly discuss the combination of radiation with antivascular agents.. "
EML4_ALK- 21994901prostate cancer;non small cell lung cancer;lung cancer;sarcoma PCR;RT-PCR - Following the discovery of the recurrent TMPRSS2:ETS fusions in prostate cancer and EML4:ALK in non-small-cell lung cancer, it is now accepted that fusion genes not only are the hallmark of haematological malignancies and sarcomas, but also play an important role in epithelial cell carcinogenesis. /// "Following the discovery of the recurrent TMPRSS2:ETS fusions in prostate cancer and EML4:ALK in non-small-cell lung cancer, it is now accepted that fusion genes not only are the hallmark of haematological malignancies and sarcomas, but also play an important role in epithelial cell carcinogenesis. "
EML4_ALK- 23324244- - - [Mechanisms of resistance to crizotinib in patients with transforming EML4-ALK fusion gene]. /// [Mechanisms of resistance to crizotinib in patients with transforming EML4-ALK fusion gene]..
EML4_ALK- 23083517squamous cell carcinoma - - Can we eliminate squamous cell carcinoma of the lung from testing of EML4-ALK fusion gene?.
EML4_ALK- 26666609- - - Alternate-day Treatment with Crizotinib for Drug-induced Esophagitis and Liver Damage in a Patient with EML4-ALK Fusion Gene-positive Lung Adenocarcinoma..
EML4_ALK- 24842630lung cancer - - Identification of a novel HLA-A 02:01-restricted cytotoxic T lymphocyte epitope derived from the EML4-ALK fusion gene.. /// The EML4-ALK fusion gene was recently identified in a subset of non-small cell lung cancers (NSCLCs). /// In this study we searched for HLA-A 02:01- and HLA-A 24:02?restricted epitopes derived from EML4-ALK by screening predicted EML4-ALK?derived candidate peptides for the induction of tumor?reactive CTLs. /// This CTL clone specifically recognized peptide?pulsed T2 cells and H2228 cells expressing HLA-A 02:01 and EML4-ALK that had been treated with IFN-? 48 h prior to examination. /// Nine EML4-ALK?derived peptides were selected by a computer algorithm based on a permissive HLA-A 02:01 or HLA-A 24:02 binding motif.
EML4_ALK- 23328135small cell carcinoma;squamous cell carcinoma;lung cancer;adenocarcinoma - - Samples from 2 patients were evaluated for EML4-ALK gene rearrangements, both of which were adequate for analysis. /// "We sought to evaluate the adequacy of ENB-obtained samples for histologic subtyping of lung cancer, epidermal growth factor receptor (EGFR) mutations, and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocations." /// "ENB is effective at obtaining tissue samples adequate for histologic subtyping, EGFR mutation, and EML4-ALK translocation analysis.. " /// "We sought to evaluate the adequacy of ENB-obtained samples for histologic subtyping of lung cancer, epidermal growth factor receptor (EGFR) mutations, and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocations. " /// Tissue adequacy for EGFR mutation and/or EML4-ALK analyses was also reviewed.
EML4_ALK- 26682573non small cell lung cancer;lung cancer - - Alectinib is a highly selective ALK inhibitor and shows promising efficacy in non-small cell lung cancers (NSCLC) harboring the EML4-ALK gene rearrangement.
EML4_ALK- 22787411non small cell lung cancer - - Maintenance therapy is emerging as a new option for patients, as are targeted therapies for particular molecular subtypes of nsclc, such as crizotinib in tumours harbouring the EML4-ALK gene rearrangement..
EML4_ALK- 20926402non small cell lung cancer;lung cancer - - Here, we review perspectives of biomarker-driven personalized therapy in NSCLC, with particular reference to the detection of EML4-ALK gene rearrangements.
EML4_ALK- 23265700non small cell lung cancer;lung cancer - - Targeted therapy based on the presence of activating epidermal growth factor receptor (EGFR) activating mutations or EML4-ALK gene rearrangement is becoming standard practice with high median survival rates, up to 30 months.
EML4_ALK- 22912387lung cancer - - By making use of the Ba/F3 cell line model, we analyzed the cytotoxic efficacy of ALK kinase inhibitors as a function of different EML4-ALK fusion variants v1, v2, v3a, and v3b as well as of three artificially designed EML4-ALK deletion constructs and the ALK fusion genes KIF5b-ALK and NPM1-ALK.
EML4_ALK- 22568572non small cell lung cancer;lung cancer - - EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) was recently identified as a transforming fusion gene in non-small cell lung cancer (NSCLC). /// "A small-molecule tyrosine kinase inhibitor of ALK, crizotinib, shows pronounced clinical activity in the treatment of patients with NSCLC positive for EML4-ALK, and it has rapidly entered into daily clinical practice." /// "A small-molecule tyrosine kinase inhibitor of ALK, crizotinib, shows pronounced clinical activity in the treatment of patients with NSCLC positive for EML4-ALK, and it has rapidly entered into daily clinical practice. "
EML4_ALK- 25265433non small cell lung cancer;lung cancer FISH;PCR;RT-PCR - Among the mutations described in non-small cell lung carcinoma is a rearrangement resulting from an inversion within chromosome 2p leading to the formation of a fusion gene, echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK). /// The role of immunohistochemical analysis in the evaluation of EML4-ALK gene rearrangement in lung cancer.. /// "Sensitivity of the EML4-ALK IHC stain is excellent (100%) but due to its suboptimal specificity, IHC cannot reliably supplant FISH analysis for the detection of ALK gene rearrangements. " /// "One of the 4 FISH-negative, IHC-positive cases harbored an EML4-ALK rearrangement by RT-PCR yielding 3 false-positive results overall. " /// "The sensitivity and specificity of the EML4-ALK IHC stain compared with ALK FISH analysis were 100% and 96%, respectively. " /// "A total of 110 non-small cell lung carcinoma cases (63 surgical/biopsy and 47 cytology specimens), previously tested for ALK gene rearrangements by FISH [7 (6.4%) positive for the rearrangement], were probed for the EML4-ALK fusion protein using a monoclonal EML4-ALK antibody, clone 5A4. " /// Immunohistochemistry (IHC) using an antibody directed against the EML4-ALK fusion protein provides a widely available alternative method of detection.
EML4_ALK- 24133367non small cell lung cancer;lung cancer;adenocarcinoma - - RET fusion genes were mutually exclusive from EGFR, KRAS mutations and EML4-ALK fusion.
EML4_ALK- 25157770- - - The demographic data and clinical outcomes of patients with the ROS1 fusion gene were compared with those of patients without the ROS1 fusion gene, including those with the EGFR mutation, EML4-ALK fusion, KRAS mutation, and quadruple-negative patients.
EML4_ALK- 26544515non small cell lung cancer PCR;RT-PCR - Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer.. /// Monitoring of EML4-ALK rearrangements in the platelets of one patient over a period of 30 months revealed crizotinib resistance two months prior to radiographic disease progression. /// "However, despite initial response, most patients will eventually relapse, and monitoring EML4-ALK rearrangements over the course of treatment may help identify these patients. " /// RT-PCR demonstrated 65% sensitivity and 100% specificity for the detection of EML4-ALK rearrangements in platelets. /// "Platelets are a valuable source for the non-invasive detection of EML4-ALK rearrangements and may prove useful for predicting and monitoring outcome to crizotinib, thereby improving clinical decisions based on radiographic imaging alone.. " /// Non-small-cell lung cancers harboring EML4-ALK rearrangements are sensitive to crizotinib.
EML4_ALK- 22908099non small cell lung cancer;lung cancer FISH;PCR;RT-PCR - EML4-ALK is a lung cancer oncogene, and ALK inhibitors show marked therapeutic efficacy for tumors harboring this fusion gene. /// Screening for EML4-ALK and KIF5B-ALK with our RT-PCR system identified EML4-ALK transcripts in 36 samples (4.46%) from 32 individuals (4.24%). /// We here tested whether reverse transcription PCR (RT-PCR)-based detection of EML4-ALK is a sensitive and reliable approach. /// We propose that diagnostic tools for EML4-ALK should be selected in a manner dependent on the available specimen types. /// A prospective PCR-based screening for the EML4-ALK oncogene in non-small cell lung cancer..
EML4_ALK- 24674157non small cell lung cancer;lung cancer FISH;PCR;RT-PCR - Considering a threshold of 100 reads for 3' ALK region as indirect indicator of EML4-ALK rearrangement, there was 100% concordance between the novel multiplex ALK RNA-seq approach and ALK FISH among all 32 NSCLC samples. /// "While fluorescent in situ hybridization (FISH) is the current gold standard for detection of EML4-ALK rearrangements, several limitations exist including high costs, time-consuming evaluation and somewhat equivocal interpretation of results. " /// "Two lung cancer cell lines and a selected series of 32 NSCLC samples including 11 cases with EML4-ALK rearrangement were analyzed with this novel approach in comparison to ALK FISH, ALK qRT-PCR and EML4-ALK RT-PCR. " /// We developed a novel approach for indirect detection of EML4-ALK rearrangements based on 454 massive parallel sequencing after reverse transcription and subsequent multiplex amplification (multiplex ALK RNA-seq) which takes advantage of unbalanced expression of the 5' and 3' ALK mRNA regions. /// "Multiplex ALK RNA-seq is a sensitive and specific method for indirect detection of EML4-ALK rearrangements, and can be easily implemented in panel based molecular diagnostic work-up of NSCLCs by massive parallel sequencing.. " /// "The H2228 cell line with known EML4-ALK rearrangement showed 171 and 729 reads for 5' and 3' ALK regions, respectively, demonstrating a clearly unbalanced expression pattern. " /// Sensitive and specific detection of EML4-ALK rearrangements in non-small cell lung cancer (NSCLC) specimens by multiplex amplicon RNA massive parallel sequencing..
EML4_ALK- 23226067non small cell lung cancer;lung cancer - - More recently, the presence of a fusion gene, echinoderm microtubule-associated protein-like 4 - anaplastic lymphoma kinase (EML4-ALK), was identified as the driver mutation in yet another subgroup of patients, and subsequent studies have led to approval of crizotinib in this group of patients. /// "More recently, the presence of a fusion gene, echinoderm microtubule-associated protein-like 4 - anaplastic lymphoma kinase (EML4-ALK), was identified as the driver mutation in yet another subgroup of patients, and subsequent studies have led to approval of crizotinib in this group of patients. " /// "In this article, efforts in personalizing delivery of care based on the histological subtypes of lung cancer and the role of K-RAS and EGFR mutations, EML4/ALK translocation, and ERCC1 (excision repair cross-complementing 1) and EGFR expression in choosing appropriate treatments for patients with advanced lung cancer are discussed. "
EML4_ALK- 18414414non small cell lung cancer;breast cancer;lung ca - - Our data suggest that the EML4-ALK fusion transcript is not present in gastrointestinal or breast cancers and is specific to NSCLC.. /// "Only one of the lung cancer samples tested positive for the EML4-ALK fusion transcript, whereas none were detected in 555 gastrointestinal and 90 breast cancer cases. " /// EML4-ALK fusion transcript is not found in gastrointestinal and breast cancers.. /// We evaluated the expression of the EML4-ALK transcript in 104 lung cancer cases and in 645 gastrointestinal and breast cancer samples. /// The EML4-ALK (EML4: echinoderm microtubule-associated-protein-like 4.
EML4_ALK- 26505450non small cell lung cancer;lung cancer;adenocarcinoma - - Echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) gene rearrangements and epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) have been intensively studied.
EML4_ALK- 21415216non small cell lung cancer;lung cancer - - EML4-ALK (echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase) was recently identified as a transforming fusion gene in non-small cell lung cancer. /// We established NIH 3T3 cells that stably express variant 1 or 3 of EML4-ALK and examined the signaling molecules that function downstream of EML4-ALK. /// "Forced expression of EML4-ALK induced marked activation of extracellular signal-regulated kinase (ERK) and STAT3, but not that of AKT. " /// The purpose of the present study was to characterize the mechanism of malignant transformation by EML4-ALK. /// "Inhibition of ERK or STAT3 signaling resulted in substantial attenuation of the proliferation of cells expressing either variant of EML4-ALK, suggesting that these signaling pathways function downstream of EML4-ALK in lung cancer cells. "
EML4_ALK- 23279872lung cancer;adenocarcinoma - - Both tumors also harbored the EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) fusion gene (variant 3a+b). /// Solitary pulmonary metastasis from lung cancer harboring EML4-ALK after a 15-year disease-free interval..
EML4_ALK- 27045755non small cell lung cancer;lung cancer PCR - The third patient had three additional fusion genes, of which two were derived from the same chromosomal region as the EML4-ALK.
EML4_ALK- 21562939non small cell lung cancer - - NSCLC with the EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) fusion gene is also more likely to occur in never smokers and in those with adenocarcinoma histology, and is expected to benefit from ALK inhibitors.
EML4_ALK- 22771825non small cell lung cancer;lung cancer - - Within the EML4-ALK cohort, patients with variants 1 or 3 of the fusion gene were predominant and did not appear to differ in their sensitivity to the platinum-based regimens. /// "Platinum-based combination chemotherapy showed similar efficacies in the EML4-ALK, EGFR mutation, and wild-type cohorts in terms of response rate and progression-free survival, and overall survival in the EML4-ALK cohort closely resembled that in the wild-type cohort. " /// "Among 200 patients with advanced nonsquamous NSCLC, 18 (9.0%) were positive for EML4-ALK, 31 (15.5%) harbored EGFR mutations, and 151 (75.5%) were wild type for both abnormalities. " /// The efficacy of platinum-based chemotherapy was compared between patients with advanced nonsquamous NSCLC who harbor EML4-ALK and those who harbor EGFR mutations and those with neither molecular abnormality. /// The EML4-ALK fusion oncogene represents a recently identified molecular target in a subset of patients with non-small-cell lung cancer (NSCLC).
EML4_ALK- 21206384lung cancer;mesothelioma - - Several studies on the development and testing of new molecular diagnostic tests to detect epidermal growth factor receptor tyrosine kinase mutations and EML4-ALK (Echinoderm Microtubule-associated Protein like 4 Anaplastic Lymphoma Receptor Tyrosine Kinase) fusion gene were presented as well..
EML4_ALKt(2;5) / 19459784neuroblastoma - - Recent reports of the EML4 (echinoderm microtubule-associated protein like 4)-ALK oncoprotein in NSCLC (non-small cell lung cancer), together with the identification of activating point mutations in neuroblastoma, have highlighted ALK as a significant player and target for drug development in cancer.
EML4_ALK- 23741400non small cell lung cancer;lung cancer;adenocarcinoma FISH;PCR;RT-PCR - The aim of this study was to compare the diagnostic accuracy of FISH, immunohistochemistry (IHC), and real-time quantitative RT-PCR (QPCR) methodologies for detection of EML4-ALK rearrangement in NSCLC and to appraise immunohistochemistry as a pre-screening tool. /// "However, assessing EML4-ALK rearrangement in NSCLC remains challenging in routine pathology practice. "
EML4_ALK- 22791881non small cell lung cancer;lung cancer FISH;PCR;RT-PCR - In addition, six novel ALK fusion variants were identified, including one KIF5B-ALK (E17;A20) and five EML4-ALK variants (E6a;A19, E6a/b ins 18;A20, E17b ins 39;A20, E10a/b, E13;A20, and E17 ins 65;A20).
EML4_ALK- 24633422lung cancer;neuroblastoma - - This is the first report of the whole genomic sequencing of a papillary thyroid cancer in which we identified an EML4-ALK translocation of a TRAPP oncogene mutation. /// Whole-genome sequencing of an aggressive BRAF wild-type papillary thyroid cancer identified EML4-ALK translocation as a therapeutic target.. /// "The EML4-ALK translocation has been reported in approximately 5 % of lung cancers, as well as in pediatric neuroblastoma, and is a therapeutic target for crizotinib. "
EML4_ALK- 26037683lung cancer;adenocarcinoma - - We report the case of a 54-year-old woman with a primary bronchial adenocarcinoma with an EML4-ALK translocation.
EML4_ALK- 25247338non small cell lung cancer;lung cancer - - The incredible story of ALK rearranged tumors, with the rapid Food and Drug Administration approval of Crizotinib after only 4 years from the discovery of EML4-ALK translocation in NSCLC, has profoundly influenced the concept of drug development in NSCLC, paving the way to a novel series of molecularly selected studies with specific inhibitors.
EML4_ALK- 24138719non small cell lung cancer;lung cancer - - EGFR activating mutations, EML4/ALK translocation, ROS1 rearrangements) in a selected population of patients affected by non small cell lung cancer (NSCLC) translated into effective treatments for this small but well defined fraction of patients, driven by the use of predictive biomarkers of efficacy for targeted agents.
EML4_ALK- 24759083lung cancer - - Here we report the application of CRISPR/Cas technology to successfully generate several types of chromosomal rearrangements implicated as driver events in lung cancer, including the CD74-ROS1 translocation event and the EML4-ALK and KIF5B-RET inversion events.
EML4_ALK- 24070465non small cell lung cancer;lung cancer - - Elderly patients affected by NSCLC harboring the EML4-ALK translocation could benefit mostly from a treatment with an oral inhibitor of such a rearrangement (crizotinib).
EML4_ALK- 24706829lung cancer - - Crystal structure of EML1 reveals the basis for Hsp90 dependence of oncogenic EML4-ALK by disruption of an atypical ?-propeller domain.. /// The Hsp90-sensitive EML4-ALK variants are exceptions to the rule that oncogenic fusion proteins involve breakpoints in disordered regions of both partners. /// Mapping the characteristic breakpoints of each EML4-ALK variant onto our structure indicates that the EML4 TAPE domain is truncated in many variants in a manner likely to make the fusion protein structurally unstable.
EML4_ALK- 22311682non small cell lung cancer;lung cancer - - The biology and clinical features of non-small cell lung cancers with EML4-ALK translocation..
EML4_ALK- 25178493non small cell lung cancer - - Adenocarcinoma of the lung with EML4-ALK translocation is a rare subtype of Non Small-Cell Lung Cancer (NSCLC) that has recently shown to benefit from treatment with crizotinib.
EML4_ALK- 25588859non small cell lung cancer;lung cancer;adenocarcinoma - - EML4-ALK translocations are rare events associated with specific clinicopathological features, such as never or light smoking history, young age and adenocarcinoma with signet ring or acinar histology.
EML4_ALK- 23328551non small cell lung cancer;non small cell lung cancer;small cell lung cancer - - These results suggest that ALK inhibitors may be safe and effective in critically ill patients on mechanical ventilation for respiratory failure resulting from EML4-ALK translocated NSCLC progression..
EML4_ALK- 26850068lung cancer - - Results reported coexistence of EGFR mutation and EML4-ALK gene translocation in plasma which heavily indicated that ALK was the primary reason for progression of the liver lesions. /// Here we report a multiple metastatic NSCLC patient who was detected to have pure EGFR 19 exon deletion (negative for EML4-ALK and ROS1 in both IHC-based and sequencing assay) in the primary lesion and responded to first-line and second-line EGFR-TKI treatments (erlotinib then HY-15772). /// Metastatic EML4-ALK fusion detected by circulating DNA genotyping in an EGFR-mutated NSCLC patient and successful management by adding ALK inhibitors: a case report..
EML4_ALK- 26208325lung cancer - - Selection of NSCLC patients for targeted therapy is currently based upon the presence of sensitizing mutations in EGFR and EML4/ALK translocations.
EML4_ALK- 23612660non small cell lung cancer;lung cancer FISH;PCR;RT-PCR - These cells were more sensitive to crizotinib, an ALK inhibitor compared with PC-9 and H460 cells without EML4-ALK rearrangement. /// "In situ proximity ligation assay (PLA) originally developed for precise detection and quantification of proteins by dual recognition and amplification process was used for sensitive detection of EML4-ALK fusion oncoprotein in NSCLC cell lines (ALK negative cell: PC-9 and H460, ALK positive cell: H3122 and H2228)." /// Sensitive detection of EML4-ALK fusion oncoprotein of lung cancer by in situ proximity ligation assay. /// EML4-ALK oncogene and protein in lung cancer cells were confirmed by multiplex RT-PCR and Western blots. /// We detected 117 kDa variant 1 of EML4-ALK in H3122 and 90 kDa variant 3 of EML4-ALK in H2228. /// EML4-ALK fusion oncogene has emerged as a novel molecular target in non-small cell lung cancer (NSCLC). /// Highly specific and sensitive detection of EML4-ALK fusion oncoprotein is possible by in situ PLA method suggesting its clinical application.. /// Sensitive detection of EML4-ALK fusion oncoprotein of lung cancer by in situ proximity ligation assay.. /// "In situ proximity ligation assay (PLA) originally developed for precise detection and quantification of proteins by dual recognition and amplification process was used for sensitive detection of EML4-ALK fusion oncoprotein in NSCLC cell lines (ALK negative cell: PC-9 and H460, ALK positive cell: H3122 and H2228). "
EML4_ALK- 24926551lung cancer;adenocarcinoma RT-PCR - The most common abnormality was EGFR mutation (29%), followed by EML4-ALK rearrangement (5%), KRAS mutation, and EGFR amplification (4%, each).
EML4_ALK- 21036415adenocarcinoma FISH;RT-PCR - One new EML4-ALK fusion variant was identified. /// "A recent report suggesting an association between Ad-SRCC and EML4-ALK fusion prompted us to undertake a histological, immunohistochemical, and molecular analysis of 10 cases of primary Ad-SRCC identified out of 699 lung adenocarcinomas (1.4%). "
EML4_ALK- 26045865non small cell lung cancer;lung cancer;adenocarc - - EML4-ALK rearrangement is detected in 2% to 7% of lung adenocarcinomas, these tumors are sensitive to crizotinib.
EML4_ALK- 27033383non small cell lung cancer;lung cancer;adenocarcinoma PCR - The frequency of EML4-ALK mutation was higher in the early stage patients with solid predominant tumors and invasive mucinous adenocarcinomas (P=0.025, P=0.014, respectively).
EML4_ALK- 23486270- - - Ineffectiveness of crizotinib on brain metastases in two cases of lung adenocarcinoma with EML4-ALK rearrangement. /// Ineffectiveness of crizotinib on brain metastases in two cases of lung adenocarcinoma with EML4-ALK rearrangement..
EML4_ALK- 26377037lung cancer - - In these patients, EGFR and KRAS mutations as well as EML4/ALK rearrangements are recognized as "drivers" and as targets for therapy. /// "24.8% of patients were EGFR mutated (31/125), 21.6% were KRAS mutated (27/125) and 13.6% hadan EML4/ALK rearrangement (17/125). " /// The presence of EML4/ALK rearrangement was associated with an increased PE risk.. /// "Data on the oncogene drivers (EGFR, KRAS or EML4/ALK) of the same patients were collected." /// "Data on the oncogene drivers (EGFR, KRAS or EML4/ALK) of the same patients were collected. "
EML4_ALK- 25408655- - - Although the lung biopsy sample was insufficient for molecular testing, hybrid capture-based comprehensive genomic profiling (FoundationOne) identified an EML4-ALK rearrangement in the RUE lesion. /// A Poorly Differentiated Malignant Neoplasm Lacking Lung Markers Harbors an EML4-ALK Rearrangement and Responds to Crizotinib.. /// "Although the lung biopsy sample was insufficient for molecular testing, hybrid capture-based comprehensive genomic profiling (FoundationOne) identified an EML4-ALK rearrangement in the RUE lesion. "
EML4_ALK- 25750344non small cell lung cancer;lung cancer;adenocarcinoma - - Patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) gene mutations or echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangement often have a better prognosis when they are treated with specific inhibitors than when treated with cytotoxic agents. /// Patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) gene mutations or echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangement often have a better prognosis when they are treated with specific inhibitors than when treated with cytotoxic agents.
EML4_ALK- 26677785non small cell lung cancer;lung cancer - - Three ALK+ NSCLC patients treated between 2011 and 2014 (two males, two never smokers, age range 20-54years, all echinoderm microtubule-associated protein-like 4/ALK rearrangement), were diagnosed with progressing cerebral disease while receiving crizotinib. /// "Three ALK+ NSCLC patients treated between 2011 and 2014 (two males, two never smokers, age range 20-54years, all echinoderm microtubule-associated protein-like 4/ALK rearrangement), were diagnosed with progressing cerebral disease while receiving crizotinib. "
EML4_ALK- 26398829- - - A Case of Atypical Carcinoid: Harboring Variant 3a/b EML4-ALK Rearrangement. /// A Case of Atypical Carcinoid: Harboring Variant 3a/b EML4-ALK Rearrangement..
EML4_ALK- 25119973non small cell lung cancer;lung cancer - - All lung cancer patients with mutant epidermal growth factor receptor (EGFR) or rearranged EML4-ALK eventually develop acquired resistance to treatment. /// "Patients with mutant EGFR or rearranged EML4-ALK non-small cell lung cancer (NSCLC) and acquired resistance to tyrosine kinase inhibitors were included in a retrospective study to determine the percentage of patients who underwent rebiopsy and whether rebiopsy would have been possible, or not, in the remaining patients. " /// All lung cancer patients with mutant epidermal growth factor receptor (EGFR) or rearranged EML4-ALK eventually develop acquired resistance to treatment.
EML4_ALK- 26739511lung cancer;adenocarcinoma - - A total of 618 patients had mutations in EGFR or KRAS gene as well as rearrangement of EML4-ALK. /// A total of 618 patients had mutations in EGFR or KRAS gene as well as rearrangement of EML4-ALK. /// "Here, we analyzed the mutational frequency of EGFR and KRAS gene, as well as EML4-ALK rearrangement, and summarized the clinicopathological characters of Chinese lung cancer patients. " /// "Rearrangement of EML4-ALK was more common in non-tobacco-using male patients, who also exhibited a higher likelihood of visceral pleura invasion." /// "Rearrangement of EML4-ALK was more common in non-tobacco-using male patients, who also exhibited a higher likelihood of visceral pleura invasion. "
EML4_ALK- 23060582non small cell lung cancer;lung cancer - - Characteristics were compared among patients classified positive for EGFR mutations, EML4-ALK rearrangement, or patients who were double-negative for these changes. /// EGFR mutations and the EML4-ALK rearrangements were detected in substantial proportions of patients with locally advanced NSCLC. /// Clinical outcomes of thoracic radiotherapy for locally advanced NSCLC with EGFR mutations or EML4-ALK rearrangement.. /// We identified 11 (29.7%) patients with EGFR mutations and 3 (8.1%) with an EML4-ALK rearrangement.
EML4_ALK- 25819217non small cell lung cancer;lung cancer - - The identification of the EML4-ALK rearrangement in 5% of NSCLC enhanced the development of 1st generation ALK inhibitors such as crizotinib.
EML4_ALK- 25434695non small cell lung cancer;lung cancer;adenocarc - - We showed that younger age at diagnosis was the only independent variable associated with EML4-ALK rearrangements (odds ratio (OR) per 5 years' increment, 0.68. /// "In this cross-sectional study, 1160 NSCLC patients were prospectively enrolled and genotyped for EML4-ALK rearrangements and EGFR mutations. " /// These findings should assist clinicians in assessing the likelihood of EML4-ALK rearrangements and EGFR mutations and understanding their biological implications in NSCLC.
EML4_ALK- 25653542lung cancer;adenocarcinoma;mesothelioma - - One of these new cell lines bears EML4-ALK rearrangement variant 2, two lung cancer cell lines bear different KRAS mutations at codon 12, and known single nucleotide polymorphism variants were identified in these cell lines.
EML4_ALK- 23733083non small cell lung cancer;lung cancer - - EGFR activating mutations (exons 18 to 21) and EML4-ALK rearrangement are clinically important markers able to select NSCLC patients which benefit from EGFR or ALK tyrosine kinase inhibitors (gefitinib, erlotinib, crizotinib).
EML4_ALK- 26520640non small cell lung cancer;lung cancer - - We prospectively addressed whether EGFR and KRAS mutations, EML4-ALK, ROS1 and RET rearrangements, or wild-type (WT), affects radiosurgery outcomes and overall survival (OS) in non-small cell lung cancer (NSCLC) patients with brain metastases (BM).
EML4_ALK- 23386065non small cell lung cancer;lung cancer - - ALK rearrangement results in an aberrant EML4-ALK fusion oncogene that constitutively activates ALK tyrosine kinase, resulting in inhibition of apoptosis and promotion of tumor cell proliferation.
EML4_ALK- 25373537lung cancer;adenocarcinoma - - Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) inhibitors are effective and useful agents for treating patients who harbor EGFR-TKI-sensitive mutations or EML4-ALK rearrangement. /// EGFR mutations and EML4-ALK rearrangement were assessed in all of the patients.
EML4_ALK- 24419060non small cell lung cancer;lung cancer - - Echinoderm microtubule-associated protein like 4 (EML4)-ALK, which is derived from the rearrangement of ALK and EML4 genes, has been validated as a therapeutic target in a subset of patients with NSCLC. /// "Finally, ASP3026 exhibited potent antitumor activity against cells expressing EML4-ALK with a mutation in the gatekeeper position (L1196M) that confers crizotinib resistance. " /// "In mice xenografted with NCI-H2228 cells expressing EML4-ALK, orally administered ASP3026 was well absorbed in tumor tissues, reaching concentrations >10-fold higher than those in plasma, and induced tumor regression with a wide therapeutic margin between efficacious and toxic doses. "
EML4_ALK- 26525068lung cancer - - We report here a case of a very young woman with diagnosis of early-stage lung adenocarcinoma harboring EML4-ALK rearrangement.
EML4_ALK- 26018277non small cell lung cancer;lung cancer - - To evaluate the therapeutic effects of different therapeutic regimens for non-small-cell lung cancer (NSCLC) with or without EML4-ALK rearrangement. /// Twenty-one ALK-positive and 50 ALK-negative NSCLC patients who received voluntarily EML4-ALK testing and 75 NSCLC patients without AL testing were enrolled in this study.
EML4_ALK- 21288922anaplastic large cell lymphoma;non small cell lung cancer;lung cancer;ly - - This review focuses on ALK rearrangements in NSCLC, starting with the discovery of the EML4-ALK fusion oncogene, and culminating in the recent validation of ALK as a therapeutic target in patients with ALK-rearranged NSCLC.
EML4_ALK- 24019783lung cancer - - Molecular testing revealed that his tumor had an echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangement.
EML4_ALK- 24758501non small cell lung cancer;adenocarcinoma - - Besides EGFR mutations, EML4-ALK rearrangement is also being analysed and there is potential in analysing BRAF mutations as well.
EML4_ALK- 25101240non small cell lung cancer;lung cancer - - Tumors harboring a rearranged EML4-ALK fusion oncogene are highly sensitive to therapy with ALK-targeted inhibitors.
EML4_ALK- 26200283squamous cell carcinoma - - A Case of Squamous Cell Carcinoma Harboring an EML4-ALK Rearrangement that Was Unsuccessfully Treated with the ALK Inhibitor Alectinib..
EML4_ALK- 25096400non small cell lung cancer;lung cancer - - Sensitivity of the H3122 NSCLC cell line (EML4-ALK rearrangement) to ALK inhibitors (crizotinib or alectinib) was investigated during a normoxic or hypoxic state using an MTT assay. /// "However, some patients with EML4-ALK rearrangements respond poorly to crizotinib. " /// Our findings indicate that hypoxia induces resistance to ALK inhibitors in NSCLC with an EML4-ALK rearrangement via the EMT.
EML4_ALK- 26958507non small cell lung cancer;lung cancer - - We also present ongoing studies that aim to address potential causes for mortality in the dose escalation arm through adaptive or proton therapy, and are also leveraging additional concurrent systemic agents such as tyrosine kinase inhibitors (TKIs) for EGFR-activating mutations or EML4-ALK rearrangements, and poly (ADP-ribose) polymerase (PARP) inhibitors.
EML4_ALK- 22282308lung cancer;adenocarcinoma - - The majority of lung adenocarcinoma patients with epidermal growth factor receptor- (EGFR) mutated or EML4-ALK rearrangement-positive tumors are sensitive to tyrosine kinase inhibitors.
EML4_ALK- 21767331non small cell lung cancer;lung cancer - - In the present study, we report on three cases harboring EML4-ALK rearrangement who were enrolled in the trial (A8081001, NCT00585195). /// It has been demonstrated that NSCLC driven by EML4-ALK is strongly addicted to this fusion-type oncokinase.
EML4_ALK- 24828670neuroendocrine carcinoma - - A case of large-cell neuroendocrine carcinoma harboring an EML4-ALK rearrangement with resistance to the ALK inhibitor crizotinib..
EML4_ALK- 25489176renal cell carcinoma - - Computer aided molecular docking data show Tivozanib and Lapatinib bind EML4-ALK with high score. /// Additional data on these compounds for use in EML4-ALK positive NSCLC will provide evidence for use in patients treated with crizotinib. /// Molecular docking studies shows tivozanib and lapatinib as potential inhibitors of EML4-ALK translocation mediated fusion protein in non small cell lung cancer. /// Molecular docking studies shows tivozanib and lapatinib as potential inhibitors of EML4-ALK translocation mediated fusion protein in non small cell lung cancer.. /// This led to successful evidence of using tyrosine kinase inhibitors (TKIs) over the standard platinum doublet based chemotherapy as the first line treatment in the metastatic setting.The rearrangements of fusion protein EML4-ALK in NSCLC lead to the use of crizotinib for this class of tumors.
EML4_ALK- 25348872adenosquamous carcinoma PCR - Based on the biobanking system, in conjunction with the clinic and pathology lab, we developed a genotyping panel designed to assess 24 mutations in 10 genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, HER2 and DDR2), EGFR, MET, PIK3CA, FGFR1 and FGFR2 copy numbers, and EML4-ALK and ROS1 translocations, using pyrosequencing plus capillary electrophoresis, quantitative polymerase chain reaction (PCR) and reverse-transcription PCR, respectively. /// "Based on the biobanking system, in conjunction with the clinic and pathology lab, we developed a genotyping panel designed to assess 24 mutations in 10 genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, HER2 and DDR2), EGFR, MET, PIK3CA, FGFR1 and FGFR2 copy numbers, and EML4-ALK and ROS1 translocations, using pyrosequencing plus capillary electrophoresis, quantitative polymerase chain reaction (PCR) and reverse-transcription PCR, respectively. "
EML4_ALK- 20406193anaplastic large cell lymphoma;non small cell lung cancer;lung cancer - - The recent reports of EML4 (echinoderm microtubule-associated protein-like 4)-ALK oncogenic proteins in non-small cell lung cancer (NSCLC) and the identification of ALK activating point mutations and gene amplification in neuroblastoma have indicated ALK as a potential major therapeutic target for human cancers.
EML4_ALK- 24199682non small cell lung cancer;lung cancer - - We sought to evaluate alternative mechanisms of resistance and preclinical strategies to overcome these in a cell line driven by EML4-ALK. /// We selected the NSCLC cell line NCI-H3122 (H3122: EML4-ALK E13;A20) and derived resistant variants that were able to grow in the presence of 1 ?M crizotinib.
EML4_ALK- 22034911non small cell lung cancer;lung cancer - - Crizotinib-resistant mutants of EML4-ALK identified through an accelerated mutagenesis screen..
EML4_ALK- 23394083non small cell lung cancer - - Crizotinib, an orally ALK and met proto-oncogene (MET) inhibitor, was very well tolerated and produced dramatic antitumor activity in early-stage trials which facilitated a faster than normal move into late-stage trials for EML4-ALK -positive NSCLC patients treatment.
EML4_ALK10p11.22 / 22194472adenocarcinoma;non small cell lung cancer - - The cancer showed no known driver mutation in EGFR or KRAS and no EML4-ALK fusion.
EML4_ALK- 25740311non small cell lung cancer;lung cancer - - Microtubule association of EML proteins and the EML4-ALK variant 3 oncoprotein require an N-terminal trimerization domain. /// "Uniquely, EML4-ALK variant 3, which includes the TD and basic region of EML4 but none of the WD40 repeats, was localized to MTs, both when expressed recombinantly and when expressed in a patient-derived NSCLC cell line (H2228)." /// "We have determined crystal structures of the coiled-coils from EML2 and EML4, which describe the structural basis of both EML self-association and oncogenic EML4-ALK activation. " /// "Uniquely, EML4-ALK variant 3, which includes the TD and basic region of EML4 but none of the WD40 repeats, was localized to MTs, both when expressed recombinantly and when expressed in a patient-derived NSCLC cell line (H2228). " /// Microtubule association of EML proteins and the EML4-ALK variant 3 oncoprotein require an N-terminal trimerization domain.. /// "Furthermore, the structure of EML4 TD may enable the development of protein-protein interaction inhibitors targeting the trimerization interface, providing a possible avenue towards therapeutic intervention in EML4-ALK NSCLC. " /// These observations prompted us to investigate MT association of EML4-ALK and EML1-ABL1 (Abelson 1) fusions in which variable portions of the EML component are present.
EML4_ALK- 24022905non small cell lung cancer;lung cancer - - To our knowledge, the present case is the second report of crizotinib-responsive brain metastases due to echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK)-rearranged NSCLC.. /// "To our knowledge, the present case is the second report of crizotinib-responsive brain metastases due to echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK)-rearranged NSCLC.. "
EML4_ALK- 23785245non small cell lung cancer;lung cancer - - Crizotinib, the first clinically available ALK tyrosine kinase inhibitor, appeared more effective compared with standard chemotherapy in NSCLC patients harboring EML4-ALK.
EML4_ALK- 24158231squamous cell carcinoma - - 95% CI, 18.7%-37.4%) were found to harbor known oncogenic mutations, including 10 with EGFR, seven with KRAS, three with PIK3CA, one with BRAF, one with HER2, one each with EGFR/PIK3CA and KRAS/PIK3CA double mutations, and two with EML4-ALK fusions.
EML4_ALK- 25592111non small cell lung cancer;lung cancer - - Synergistic effects of crizotinib and radiotherapy in experimental EML4-ALK fusion positive lung cancer..
EML4_ALK- 25714698lung cancer - - EML4-ALK, NMP-ALK, etc.).
EML4_ALK- 21258415non small cell lung cancer;lung cancer - - The Hsp90 inhibitor IPI-504 rapidly lowers EML4-ALK levels and induces tumor regression in ALK-driven NSCLC models.. /// We find EML4-ALK to be more sensitive to Hsp90 inhibition than either HER2 or mutant epidermal growth factor receptor (EGFR) with an inhibitory concentration (IC)(50) for protein degradation in the low nanomolar range. /// This degradation leads to a potent inhibition of downstream signaling pathways and to the induction of growth arrest and apoptosis in cells carrying the EML4-ALK fusion. /// "To generate a causative link between the expression of EML4-ALK and sensitivity to IPI-504, we introduced an EML4-ALK cDNA into HEK293 cells and show that the expression of the fusion protein sensitizes cells to IPI-504 both in vitro and in vivo. "
EML4_ALK- 24419423non small cell lung cancer;lung cancer - - Coexpression of equal amounts of EML4-ALK T1312fs*0 and EML4-ALK did not result in resistance to crizotinib, whereas coexpression of EML4-ALK L1196M with EML4-ALK resulted in resistance to inhibition of ALK by crizotinib. /// We analyzed 270 cases of NSCLC for ALK kinase domain splicing aberrations and in addition generated constructs with full-length echinoderm microtubule-associated protein-like 4 (EML4)-ALK (E13;A20) and a splicing isoform. /// "Unlike EML4-ALK and EML4-ALK p.L1196M, EML4-ALK T1312fs*0 did not autophosphorylate ALK or other phosphotyrosine sites. " /// ALK splicing isoforms were observed with full-length EML4-ALK in crizotinib-naive and treated NSCLCs.
EML4_ALK- 23533265non small cell lung cancer;non small cell lung cancer;lung cancer - - Here, we show that the Hsp90 inhibitor ganetespib induced loss of EML4-ALK expression and depletion of multiple oncogenic signaling proteins in ALK-driven NSCLC cells, leading to greater in vitro potency, superior antitumor efficacy, and prolonged animal survival compared with results obtained with crizotinib.
EML4_ALK- 23918070non small cell lung cancer;lung cancer - - The inhibitor of the EML4/ALK fusion protein, crizotinib, has recently become a standard second-line treatment for patients with the gene rearrangement and has promise for patients with the ROS1 rearrangement.
EML4_ALKinv(2)(p21p23) / 25337876lung cancer - - The EML4-ALK oncogene is detected in a subset of human non-small cell lung cancers (NSCLC) and is clinically relevant because it confers sensitivity to ALK inhibitors.
EML4_ALK- 20952506non small cell lung cancer;lung cancer - - In support of a functional reliance, treatment with geldanamycin-based HSP90 inhibitors resulted in rapid degradation of EML4-ALK in vitro and substantial, albeit transient, tumor regression in vivo. /// We identified EML4-ALK in complex with multiple cellular chaperones including HSP90. /// "Inhibition of ALK, PI3K/MEK, and HSP90 in murine lung adenocarcinoma induced by EML4-ALK fusion oncogene.. " /// "To evaluate potential treatment strategies for lung cancers driven by an activated EML4-ALK chimeric oncogene, we generated a genetically engineered mouse model that phenocopies the human disease where this rearranged gene arises. "
EML4_ALK- 22825000non small cell lung cancer;lung cancer - - EML4-ALK testing in non-small cell carcinomas of the lung: a review with recommendations..
EML4_ALK- 19734424anaplastic large cell lymphoma;non small cell lung cancer;follicular lymphoma - - These results indicate that EML4-ALK rearrangements are not specific of NSCLC and raise yet unsolved questions about their role in promoting human neoplasms.. /// "EML4-ALK transcripts were detected in 3/51 (5.9%) of reactive lymphoid tissues and 12/58 (20.7%) of lymphomas of different categories, including follicular lymphoma, diffuse large B-cell lymphoma and Hodgkin's disease. " /// We investigated the expression of EML4-ALK mRNA and protein in 51 reactive and 58 neoplastic lymphoid tissues. /// The EML4-ALK transcript but not the fusion protein can be expressed in reactive and neoplastic lymphoid tissues.. /// "Notably, none of these cases expressed the EML4-ALK fusion protein at Western blotting samples and immunohistochemistry." /// "Notably, none of these cases expressed the EML4-ALK fusion protein at Western blotting samples and immunohistochemistry. "
EML4_ALK- 23060067thyloid cancer;prostate cancer;leukemia;breast cancer;lung cancer;sarcoma;lymphoma - - In this review, we will summarize the histologic features of known recurrent genomic rearrangements in carcinomas, especially focusing on TMPRSS2-ERG fusion in prostate cancer, EML4-ALK in lung cancer, ETV6-NTRK3 in secretory breast cancer, RET/PTC and PAX8/PPAR?1 rearrangements in thyroid cancer.
EML4_ALK- 23910397lung cancer - - An EML4-ALK translocation was identified in an additional genetic test.
EML4_ALK- 24598368non small cell lung cancer;lung cancer - - In 2011, regulatory entities granted conditional approval to an anaplastic lymphoma kinase inhibitor (crizotinib) based on an impressive overall response rate in previously treated non-small cell lung cancer patients whose tumors harbored EML4/ALK translocations. /// "In 2011, regulatory entities granted conditional approval to an anaplastic lymphoma kinase inhibitor (crizotinib) based on an impressive overall response rate in previously treated non-small cell lung cancer patients whose tumors harbored EML4/ALK translocations. " /// Overcoming the resistance to crizotinib in patients with non-small cell lung cancer harboring EML4/ALK translocation..
EML4_ALK- 25789627- - - EML4-ALK translocation was more common in patients with younger age. /// EML4-ALK translocation was tested by Ventana method in EGFR-wild type patients (Cohort 2). /// "In Cohort 2 analysis, 29 of 295 EGFR-wild type patients (9.8%) were positive for EML4-ALK translocation. " /// "Gender and smoking status were not correlated significantly with HER2, BRAF and EML4-ALK mutations." /// "Gender and smoking status were not correlated significantly with HER2, BRAF and EML4-ALK mutations. " /// "Five oncogenic drivers, including EGFR, KRAS, BRAF, HER2 and EML4-ALK fusion mutations, were tested. "
EML4_ALK- 24754584non small cell lung cancer;lung cancer - - Combined point mutation in KRAS or EGFR genes and EML4-ALK translocation in lung cancer patients.. /// "First, a combined simultaneous KRAS mutation and EML4-ALK translocation, both in the main tumor and a bone metastasis, were observed, these mutations are assumed to mutually exclude each other. "
EML4_ALK- 23993685lung cancer - - Here, we investigated if this reduced sensitivity also contributes to resistance to crizotinib, an ALK inhibitor of lung cancer that exhibits the EML4-ALK translocation. /// "Here, we investigated if this reduced sensitivity also contributes to resistance to crizotinib, an ALK inhibitor of lung cancer that exhibits the EML4-ALK translocation. " /// Epithelial-mesenchymal transition leads to crizotinib resistance in H2228 lung cancer cells with EML4-ALK translocation.. /// "Compared with H2228 cells, the growth of H2228/CR cells was independent of EML4-ALK, and H2228/CR cells showed cross-resistance to TAE-684 (a second-generation ALK inhibitor). "
EML4_ALK- 23897899non small cell lung cancer;lung cancer - - No patients with metastases from tumors with EGFR mutations (0/164 lesions) or EML4-ALK translocations (0/61 lesions) recurred in-field. /// "This study suggests that EGFR kinase domain mutations and EML4-ALK translocations are radiosensitive NSCLC genotypes, and proposes a novel model to identify radiosensitive subtypes of NSCLC.." /// "This study suggests that EGFR kinase domain mutations and EML4-ALK translocations are radiosensitive NSCLC genotypes, and proposes a novel model to identify radiosensitive subtypes of NSCLC.. "
EML4_ALK- 24781527non small cell lung cancer;lung cancer - - Tumor genetics showed only two EGFR mutations, EGFR amplification in 17/47 samples, eight KRAS mutations, and five EML4-ALK translocations. /// "Tumor genetics showed only two EGFR mutations, EGFR amplification in 17/47 samples, eight KRAS mutations, and five EML4-ALK translocations. "
EML4_ALK- 23242444respiratory insufficiency - - Surviving respiratory insufficiency with intensive care support in a pretreated, extensively metastasized patient with an EML4-ALK translocation. /// "Surviving respiratory insufficiency with intensive care support in a pretreated, extensively metastasized patient with an EML4-ALK translocation.. "
EML4_ALK- 26775573non small cell lung cancer;lung cancer;adenocarcinoma - - The EML4-ALK translocation is found in about 5% of NSCLC and more particularly in adenocarcinoma of young non-smoking patients. /// The EML4-ALK translocation is found in about 5% of NSCLC and more particularly in adenocarcinoma of young non-smoking patients.
EML4_ALK- 24212966small cell lung cancer - - These tests should not be routinely used in selecting treatment at this time, whereas EML4/ALK translocations predict responses to specific targeted agents, the optimal assessment of this molecular abnormality has yet to be established.
EML4_ALK- 21777762non small cell lung cancer;lung cancer - - So, the EML4 - ALK translocation is accessible to a treatment by crizotinib, with response rate around 60-70%..
EML4_ALK- 26654422non small cell lung cancer;lung cancer - - In up to 5% of non-small cell lung cancer (NSCLC) patients, the EML4-ALK translocation drives tumor progression.
EML4_ALK- 21156280non small cell lung cancer;lung cancer - - It was only 3 years ago that an acquired translocation of EML4 with ALK leading to the expression of an EML4-ALK oncoprotein in non-small cell lung cancer (NSCLC) was reported. /// "Tumor cells expressing EML4-ALK are ""addicted"" to its continued function. "
EML4_ALK- 22999080adenocarcinoma - - Clinicians should be attentive of the evolution of brain metastases with patients presenting EML4-ALK translocation.. /// We report the case of an adenocarcinoma of the lung associated with metachronous miliary brain and lung metastases with an echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) gene translocation.
EML4_ALK- 21420271lung cancer;adenocarcinoma - - New molecular targets are on investigation, such as EML4-ALK translocation.
EML4_ALK- 24102046inflammatory breast carcinoma - - One of 25 patients was identified as having an EML4-ALK translocation.
EML4_ALK- 24853389non small cell lung cancer;lung cancer - - The discovery of the echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) translocation as an oncogenic driver has led to the development of novel therapies with activity in vitro and in the clinic.
EML4_ALK- 20028651lung cancer - - Personalized medicine is becoming a reality for patients with EGFR mutation as well as for the recruitment of patients in certain clinical trials (EML4-ALK translocation, KRAS mutation...).
EML4_ALK- 25841697non small cell lung cancer;breast cancer;lung cancer;melanoma - - For instance, alterations in the epidermal growth factor receptor (EGFR) domain and echinoderm microtubule associated protein-like 4- anaplastic lymphoma kinase (EML4-ALK) translocation are routinely used to guide therapeutic decisions for advanced NSCLC. /// "Several new treatments targeting EGFR family members, novel EML4-ALK inhibitors and MEK inhibitors are currently in clinical development. "
EML4_ALK- 26134230- - - Cystic Brain Metastases in NSCLC Harboring the EML4-ALK Translocation after Treatment with Crizotinib..
EML4_ALK- 26750252anaplastic large cell lymphoma;non small cell lung cancer;lung cancer;neuroblastoma;lymphoma - - Expression of ALK in normal human tissues is only found in a subset of neural cells, however it is involved in the genesis of several cancers through genetic aberrations involving translocation of the kinase domain with multiple fusion partners (e.g., NPM-ALK in anaplastic large cell lymphoma ALCL or EML4-ALK in non-small cell lung cancer) or activating mutations in the full-length receptor resulting in ligand-independent constitutive activation (e.g., neuroblastoma).
EML4_ALK- 20418096non small cell lung cancer;lung cancer - - More recently ALK inhibitors have entered clinical development and remarkably clinical efficacy has been observed in NSCLC patients harbouring EML4-ALK translocations. /// The biology and treatment of EML4-ALK non-small cell lung cancer.. /// EML4-ALK is oncogenic both in vitro and in vivo and ALK kinase inhibitors are quite effective in pre-clinical model systems. /// EML4-ALK is most often detected in never smokers with lung cancer and has unique pathologic features. /// "This review will focus on the biology, clinical characteristics, diagnosis and treatment of EML4-ALK NSCLC.. "
EML4_ALK- 22196919non small cell lung cancer;lung cancer - - A major contributor has been the discovery of molecular subtypes harbouring a critical oncogenic driver mutation, specifically sensitizing mutations in the epidermal growth factor receptor (EGFR) gene and the EML4-ALK gene translocation.
EML4_ALK- 22614968non small cell lung cancer;lung cancer - - gefitinib, erlotinib, and cetuximab for the treatment of NSCLC harboring epidermal growth factor receptor mutation or overexpression, and crizotinib for the treatment of NSCLC with the EML4-ALK fusion translocation oncogene being some examples.
EML4_ALK- 24616318non small cell lung cancer;lung cancer - - Optic neuropathy and blindness associated with crizotinib for non-small-cell lung cancer with EML4-ALK translocation..
EML4_ALK- 23728235non small cell lung cancer;lung cancer - - For example, patients with activating EGFR mutations or EML4-ALK translocations largely benefit from targeted therapies with tyrosine kinase inhibitors with better response rates and progression-free survival compared to standard chemotherapy regimens.
EML4_ALK- 26076869small cell carcinoma;lung cancer;adenocarcinoma - - The main oncogenic factors in the field of thoracic oncology are mutations of EGFR, KRAS, and EML4-ALK translocation, which are most often reported in adenocarcinomas.
EML4_ALK- 23157740lung cancer;adenocarcinoma PCR - Based on the 2004 WHO classification, mutations of KRAS (P = 0.002) and EML4-ALK (P = 0.000), rather than EGFR (P = 0.502), showed significant differences among different subtypes. /// "However, there was no association between TTF-1 expression and EML4-ALK fusions (P = 0.274)." /// "Mutations of epidermal growth factor receptor (EGFR) 18-21 exons (E18-21), KRAS 12/13 codons and EML4-ALK fusion in 212 cases of lung adenocarcinoma which underwent complete tumor resection, were detected by immunohistochemistry, PCR-amplifying and gene sequencing." /// "Based on the 2004 WHO classification, mutations of KRAS (P = 0.002) and EML4-ALK (P = 0.000), rather than EGFR (P = 0.502), showed significant differences among different subtypes. " /// "The new classification, combined with TTF-1 immunomarker, can help to predict the molecular alterations of EGFR and KRAS genes, but can not indicate the EML4-ALK fusion in lung adenocarcinoma. " /// "Mutations of epidermal growth factor receptor (EGFR) 18-21 exons (E18-21), KRAS 12/13 codons and EML4-ALK fusion in 212 cases of lung adenocarcinoma which underwent complete tumor resection, were detected by immunohistochemistry, PCR-amplifying and gene sequencing. " /// "EML4-ALK fusions were most frequently found in the solid predominant with mucin production subtype (15.4%, 6/39), followed by colloid predominant adenocarcinoma (1/7), and no significant difference of EML4-ALK fusions was found among different histological subtypes (P = 0.181). " /// "EML4-ALK fusions were found in 6.1% of lung adenocarcinoma, the most common fusion mutation was type V1 (E13. " /// "However, there was no association between TTF-1 expression and EML4-ALK fusions (P = 0.274). "
EML4_ALK- 26104888non small cell lung cancer;lung cancer PCR;RT-PCR - Furthermore, the gene mutation frequency of EML4-ALK in the resistant cells was significantly higher than that in the parent cells. /// "Furthermore, the gene mutation frequency of EML4-ALK in the resistant cells was significantly higher than that in the parent cells. " /// The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) expression was evaluated by RT-PCR and Western blot. /// Full-length sequencing method was used to compare the EML4-ALK genes in the parent and drug-resistant cells and analyze the mechanisms of drug resistance.
EML4_ALK- 22768234non small cell lung cancer;squamous cell carcinoma PCR - In a subgroup of non-smokers with adenocarcinoma, EGFR was the most frequently altered gene, with a mutation rate of 49.8%, followed by EML4-ALK (9.3%), PTEN (9.1%), PIK3CA (5.2%), c-Met (4.8%), KRAS (4.5%), STK11 (2.7%), and BRAF (1.9%).
EML4_ALK- 25735977non small cell lung cancer;non small cell lung cancer;small cell lung c - - Thus, inhibition of ERK signaling pathway could be a potential strategy in treatment of NSCLC patients with EML4-ALK translocation.. /// "Thus, inhibition of ERK signaling pathway could be a potential strategy in treatment of NSCLC patients with EML4-ALK translocation.. " /// "Here, for the first time, we showed that H1299 NSCLC cells stably expressing EML4-ALK acquire EMT phenotype, associated with enhanced invasive migration and increased expression of EMT-inducing transcription factors. " /// "However, the role of EML4-ALK in malignant transformation is not entirely clear." /// EML4-ALK induces epithelial-mesenchymal transition consistent with cancer stem cell properties in H1299 non-small cell lung cancer cells.. /// "Moreover, we found that inhibition of ERK1/2 reversed EMT induced by EML4-ALK in H1299 cells. " /// "However, the role of EML4-ALK in malignant transformation is not entirely clear. " /// "Taken together, these results suggested that EML4-ALK induced ERK activation is mechanistically associated with EMT phenotype. "
EML4_ALK- 21502504non small cell lung cancer;lung cancer PCR - Cells resistant to higher doses (1 ?M) also developed a gatekeeper mutation, L1196M, within the kinase domain, rendering EML4-ALK insensitive to crizotinib. /// Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. /// "Cells resistant to higher doses (1 ?M) also developed a gatekeeper mutation, L1196M, within the kinase domain, rendering EML4-ALK insensitive to crizotinib. " /// We found that cells resistant to intermediate doses of crizotinib developed amplification of the EML4-ALK gene. /// "Although crizotinib was ineffectual against EML4-ALK harboring the gatekeeper mutation, we observed that two structurally different ALK inhibitors, NVP-TAE684 and AP26113, were highly active against the resistant cancer cells in vitro and in vivo. " /// Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK..
EML4_ALK- 22843788non small cell lung cancer;lung cancer PCR - The expression of EML4-ALK was reduced at the transcriptional level, whereas phosphorylation of epidermal growth factor receptor (EGFR), HER2, and HER3 was upregulated, in H3122/TR cells compared with those in H3122 cells. /// "The expression of EML4-ALK was reduced at the transcriptional level, whereas phosphorylation of epidermal growth factor receptor (EGFR), HER2, and HER3 was upregulated, in H3122/TR cells compared with those in H3122 cells. " /// EGF-mediated activation of HER family signaling is associated with ALK-TKI resistance in lung cancer positive for EML4-ALK..
EML4_ALK- 23683537non small cell lung cancer;lung cancer;adenocarcinoma - - The coexistence of EGFR and ALK-EML4 gene mutations represents a rare event (about 1%) in patients with non small cell lung cancer (NSCLC) and the few cases described in the literature have all been treated by different methods.
EML4_ALK- 22617245non small cell lung cancer;lung cancer - - We selected NSCLC cell lines--A549 (KRAS G12S), NCI-H3255 (EGFR L858R), NCI-H3122 (EML4-ALK E13;A20), and HCC78 (SLC34A2-ROS1)-to evaluate the antiproliferative effects of submicromolar concentrations of the multitargeted TKIs imatinib, sorafenib, erlotinib, and crizotinib. /// "We selected NSCLC cell lines--A549 (KRAS G12S), NCI-H3255 (EGFR L858R), NCI-H3122 (EML4-ALK E13;A20), and HCC78 (SLC34A2-ROS1)-to evaluate the antiproliferative effects of submicromolar concentrations of the multitargeted TKIs imatinib, sorafenib, erlotinib, and crizotinib. "
EML4_ALK- 20075203- - - EML4-ALK fusion in lung. /// EML4-ALK fusion in lung..
EML4_ALK- 26517679non small cell lung cancer;non small cell lung cancer;lung cancer - - Here, we report that stem-like properties stem from ALK activity in EML4-ALK+ NSCLC cells. /// "Although the inhibitor crizotinib, as it blocks the kinase activity of the resulting EML4-ALK fusion protein, displays remarkable initial responses, a fraction of NSCLC cases eventually become resistant to crizotinib by acquiring mutations in the ALK domain or activating bypass pathways via EGFR, KIT, or KRAS." /// "Although the inhibitor crizotinib, as it blocks the kinase activity of the resulting EML4-ALK fusion protein, displays remarkable initial responses, a fraction of NSCLC cases eventually become resistant to crizotinib by acquiring mutations in the ALK domain or activating bypass pathways via EGFR, KIT, or KRAS. "
EML4_ALK- 24618813- - - Abrogation of EML4-ALK in H2228 cells profoundly reduced signaling capacity of the rapamycin-sensitive mTOR pathway leading to G 1 cell cycle arrest and mitochondrial hyperpolarization, a metabolic perturbation linked to mTOR inhibition. /// "Abrogation of EML4-ALK in H2228 cells profoundly reduced signaling capacity of the rapamycin-sensitive mTOR pathway leading to G 1 cell cycle arrest and mitochondrial hyperpolarization, a metabolic perturbation linked to mTOR inhibition. " /// "CM-118 potently abrogated hepatocyte growth factor (HGF)-induced c-Met phosphorylation and cell migration, phosphorylation of ALK, EML4-ALK, and ALK resistance mutants in transfected cells. "
EML4_ALK- 24952482non small cell lung cancer;lung cancer - - These results suggest that Hsp90 inhibitors may overcome ligand-triggered resistance to new generation ALK inhibitors and may result in more successful treatment of NSCLC patients with EML4-ALK.. /// These results suggest that Hsp90 inhibitors may overcome ligand-triggered resistance to new generation ALK inhibitors and may result in more successful treatment of NSCLC patients with EML4-ALK.. /// Receptor ligand-triggered resistance to alectinib and its circumvention by Hsp90 inhibition in EML4-ALK lung cancer cells.. /// "Additionally, the heat shock protein 90 (Hsp90) inhibitor suppressed protein expression of ALK, MET, EGFR, and AKT, and thereby induced apoptosis in EML4-ALK NSCLC cells, even in the presence of EGFR ligands or HGF. "
EML4_ALK- 26168728- - - Development of potent ALK inhibitor and its molecular inhibitory mechanism against NSCLC harboring EML4-ALK proteins. /// "Cell based assays demonstrate our compounds downregulate the cellular signaling, such as Akt and Erk, by suppressing ALK activity to inhibit the proliferation of the cells harboring EML4-ALK. " /// Development of potent ALK inhibitor and its molecular inhibitory mechanism against NSCLC harboring EML4-ALK proteins.. /// " Here, we show the newly synthesized and potent ALK inhibitor having similar scaffold to KRCA-0008, which was reported previously, and its molecular mechanism against cancer cells harboring EML4-ALK fusion protein. "
EML4_ALK- 22553343lung cancer - - Paracrine receptor activation by microenvironment triggers bypass survival signals and ALK inhibitor resistance in EML4-ALK lung cancer cells. /// "We tested the effects of ligands produced by endothelial cells and fibroblasts, and the cells themselves, on the susceptibility of EML4-ALK lung cancer cell lines to crizotinib and TAE684, a selective ALK inhibitor active against cells with ALK amplification and gatekeeper mutations, both in vitro and in vivo." /// We determined whether microenvironmental factors trigger ALK inhibitor resistance in EML4-ALK lung cancer cells. /// EML4-ALK lung cancer cells were highly sensitive to ALK inhibitors. /// "Paracrine receptor activation by ligands from the microenvironment may trigger resistance to ALK inhibitors in EML4-ALK lung cancer cells, suggesting that receptor ligands from microenvironment may be additional targets during treatment with ALK inhibitors.. " /// "Although crizotinib, a dual tyrosine kinase inhibitor (TKI) of ALK and Met, shows dramatic effect against EML4-ALK lung cancer cells, these cells can acquire resistance to crizotinib by several mechanisms, including ALK amplification and gatekeeper mutation. " /// Paracrine receptor activation by microenvironment triggers bypass survival signals and ALK inhibitor resistance in EML4-ALK lung cancer cells.. /// "Endothelial cells and fibroblasts, which produce the EGFR ligands and HGF, respectively, decreased the sensitivity of EML4-ALK lung cancer cells to crizotinib and TAE684, respectively. " /// "We tested the effects of ligands produced by endothelial cells and fibroblasts, and the cells themselves, on the susceptibility of EML4-ALK lung cancer cell lines to crizotinib and TAE684, a selective ALK inhibitor active against cells with ALK amplification and gatekeeper mutations, both in vitro and in vivo. "
EML4_ALK- 23723294non small cell lung cancer - - Genes evaluated were TP53, EGFR, KRAS, LKB1, EML4-ALK, PTEN, BRAF, PIK3CA, and ErbB2. /// "Genes evaluated were TP53, EGFR, KRAS, LKB1, EML4-ALK, PTEN, BRAF, PIK3CA, and ErbB2. "
EML4_ALK- 20979473small cell lung cancer;lung cancer - - The EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) fusion-type tyrosine kinase is an oncoprotein found in 4 to 5% of non-small-cell lung cancers, and clinical trials of specific inhibitors of ALK for the treatment of such tumors are currently under way. /// "Here, we report the discovery of two secondary mutations within the kinase domain of EML4-ALK in tumor cells isolated from a patient during the relapse phase of treatment with an ALK inhibitor. " /// EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors..
EML4_ALK- 22443113non small cell lung cancer;lung cancer - - The echinoderm microtubule-associated protein like-4-anaplastic lymphoma kinase (EML4-ALK) fusion oncogene represents one of the newest molecular targets in NSCLC, identifying a subset of NSCLC patients characterized by distinct clinicopathological features. /// "The echinoderm microtubule-associated protein like-4-anaplastic lymphoma kinase (EML4-ALK) fusion oncogene represents one of the newest molecular targets in NSCLC, identifying a subset of NSCLC patients characterized by distinct clinicopathological features. "
EML4_ALK- 26237499non small cell lung cancer;lung cancer;hepatocel - - Lung adenocarcinoma includes recurrent activating oncogenic mutations (EGFR, EML4-ALK, ROS1) that have been associated with response to EGFR and ALK inhibitors. /// " Lung adenocarcinoma includes recurrent activating oncogenic mutations (EGFR, EML4-ALK, ROS1) that have been associated with response to EGFR and ALK inhibitors. "
EML4_ALK- 23443800non small cell lung cancer;lung cancer - - ALK inhibitor PF02341066 (crizotinib) increases sensitivity to radiation in non-small cell lung cancer expressing EML4-ALK. /// "Our findings indicate that PF02341066 acts as a radiation sensitizer in cells harboring the EML4-ALK fusion, providing a rationale for a clinical trial combining ALK inhibitor with radiation in the NSCLCs expressing ALK.." /// ALK inhibitor PF02341066 (crizotinib) increases sensitivity to radiation in non-small cell lung cancer expressing EML4-ALK.. /// "Our findings indicate that PF02341066 acts as a radiation sensitizer in cells harboring the EML4-ALK fusion, providing a rationale for a clinical trial combining ALK inhibitor with radiation in the NSCLCs expressing ALK.. " /// "To further elucidate the role of PF02341066 in tumor inhibition, we examined its effects alone and in combination with radiation on downstream signaling, apoptosis, and radiosensitivity in two NSCLC cell lines in vitro: H3122, which harbors the EML4-ALK fusion, and H460, which does not. "
EML4_ALK- 25364516lung cancer;adenocarcinoma - - Nineteen EGFR mutations (52.8%), 3 KRAS mutations (8.3%), 2 EML4-ALK fusions (5.6%) and 1 KIF5b-RET fusion (2.8%) were identified in the younger group. /// "Nineteen EGFR mutations (52.8%), 3 KRAS mutations (8.3%), 2 EML4-ALK fusions (5.6%) and 1 KIF5b-RET fusion (2.8%) were identified in the younger group. "
EML4_ALK- 22007174- - - Some examples, including BCR-Abl, EML4-ALK, and the androgen receptor, contain mutations in the target itself, which hamper binding and inhibitory functions of therapeutic agents. /// "Some examples, including BCR-Abl, EML4-ALK, and the androgen receptor, contain mutations in the target itself, which hamper binding and inhibitory functions of therapeutic agents. "
EML4_ALK- 20578368lung cancer - - [Discovery of EML4-ALK, a new gene responsible for lung cancer, and the development of molecular targeted therapy]. /// "[Discovery of EML4-ALK, a new gene responsible for lung cancer, and the development of molecular targeted therapy].. "
EML4_ALK- 23439505adenocarcinoma - - In conclusion, NFKBIA expression was silenced in adenocarcinomas without EGFR/K-ras mutations or EML4-ALK fusion, suggesting that the silencing of NFKBIA may play an important role in the carcinogenesis of adenocarcinomas independent of EGFR/K-ras mutations or EML4-ALK fusion.. /// "EGFR and K-ras mutations and EML4-ALK fusion were detected in 61 (60.5%), 1 (1.0%), and 2 (2.0%) of the 101 samples, respectively, in a completely mutually exclusive manner. " /// "We examined NFKBIA expression, mutations in the EGFR and K-ras genes, and EML4-ALK fusion in 101 resected lung adenocarcinoma samples from never-smokers. "
EML4_ALK- 23802852lung cancer - - Targetable biomarkers other than EGFR and EML4-ALK were identified in 7 of the 40 Hispanic patients (18%) and 5 of the 43 non-Hispanic white patients (12%), suggesting a similar mutational frequency. /// To identify targetable biomarkers other than EGFR and EML4-ALK in Hispanic patients with lung adenocarcinoma. /// Our highly multiplexed genotyping assay detected actionable mutations in 14% (12 of 83) more patients than would have been identified by EGFR and EML4-ALK testing alone.. /// "Targetable biomarkers other than EGFR and EML4-ALK were identified in 7 of the 40 Hispanic patients (18%) and 5 of the 43 non-Hispanic white patients (12%), suggesting a similar mutational frequency. "
EML4_ALK- 21368458lung cancer - - Transgenic mice expressing EML4-ALK in lung developed hundreds of lung cancer nodules soon after birth, but such nodules were readily eradicated upon treatment with an ALK inhibitor. /// "Transgenic mice expressing EML4-ALK in lung developed hundreds of lung cancer nodules soon after birth, but such nodules were readily eradicated upon treatment with an ALK inhibitor. " /// "We have discovered a small, fusion-type tyrosine kinase EML4-ALK that is generated through a tiny inversion within the short arm of human chromosome 2. "
EML4_ALK- 24567430non small cell lung cancer;lung cancer - - Cost effectiveness of EML4-ALK fusion testing and first-line crizotinib treatment for patients with advanced ALK-positive non-small-cell lung cancer. /// Cost effectiveness of EML4-ALK fusion testing and first-line crizotinib treatment for patients with advanced ALK-positive non-small-cell lung cancer.. /// EML4-ALK fusion testing in stage IV nonsquamous NSCLC with crizotinib treatment for ALK-positive patients is not cost effective in the setting of high drug costs and a low biomarker frequency in the population.. /// ALK-targeted therapy with crizotinib offers significant improvement in clinical outcomes for the treatment of EML4-ALK fusion-positive non-small-cell lung cancer (NSCLC). /// We estimated the cost effectiveness of EML4-ALK fusion testing in combination with targeted first-line crizotinib treatment in Ontario.
EML4_ALK- 25496960- - - Lung adenocarcinoma harboring concomitant EGFR mutation and EML4-ALK fusion that benefits from three kinds of tyrosine kinase inhibitors: a case report and literature review..
EML4_ALK- 20855837adenocarcinoma - - Forty-one tumors harbored EGFR mutations, three harbored EML4-ALK fusions, two harbored HER2 insertions, and one harbored a KRAS mutation.
EML4_ALK- 25669975cervical cancer;squamous cell carcinoma PCR;RT-PCR - No mutations were detected in AKT1 or BRAF, and the fusions FGFR1-TACC1, EML4-ALK, CCDC6-RET and KIF5B-RET were not found in any of the cancers. /// "No mutations were detected in AKT1 or BRAF, and the fusions FGFR1-TACC1, EML4-ALK, CCDC6-RET and KIF5B-RET were not found in any of the cancers. "
EML4_ALK- 24900831- - - Compound 8a displayed appreciable antitumor efficacy at the dose of 1 mg/kg in the ALK-driven BF3/EML4-ALK xenograft mice model.
EML4_ALK- 23423768squamous cell carcinoma - - The two essential requirements for pathologic specimens in the era of personalized therapies for non-small cell lung carcinoma (NSCLC) are accurate subtyping as adenocarcinoma (ADC) versus squamous cell carcinoma (SqCC) and suitability for EGFR molecular testing, as well as for testing of other oncogenes such as EML4-ALK and KRAS. /// " The two essential requirements for pathologic specimens in the era of personalized therapies for non-small cell lung carcinoma (NSCLC) are accurate subtyping as adenocarcinoma (ADC) versus squamous cell carcinoma (SqCC) and suitability for EGFR molecular testing, as well as for testing of other oncogenes such as EML4-ALK and KRAS. "
EML4_ALK- 25501361non small cell lung cancer;lung cancer;adenocarcinoma - - We retrospectively analyzed patients with EML4-ALK positive advanced NSCLC who were treated with crizotinib from May 2012 to Aug 2013. /// We retrospectively analyzed patients with EML4-ALK positive advanced NSCLC who were treated with crizotinib from May 2012 to Aug 2013. /// The EML4-ALK fusion rate and number of prior chemotherapy cycles did not appear to significantly affect the efficacy of crizotinib.
EML4_ALK- 23154565small cell lung cancer;lung cancer;adenocarcinoma - - First case of combined small-cell lung cancer with adenocarcinoma harboring EML4-ALK fusion and an exon 19 EGFR mutation in each histological component..
EML4_ALK- 23277484non small cell lung cancer;lung cancer - - EML4-ALK, PIK3CA, and MEK1 mutations occurred in NSCLC with various distinct clinicopathological characteristics. /// "EML4-ALK, PIK3CA, and MEK1 mutations were mutually exclusive. " /// "EML4-ALK, PIK3CA, and MEK1 mutations were mutually exclusive." /// "Furthermore, tumors with EML4-ALK fusions had significantly higher levels of ERCC1, a molecule with a key role in platinum drug efficacy, than tumors without EML4-ALK fusions. " /// EML4-ALK fusion was found to be of coexistence with EGFR and KRAS mutations in two cases. /// EML4-ALK fusions could serve as a significant prognostic indicator for locally advanced NSCLC.. /// "Moreover, multivariate analysis indicated that in stage IIIA NSCLC EML4-ALK fusion was the only significant indicator for poor DFS (P < 0.001). " /// "Of 488 patients with NSCLC, 28 had EML4-ALK fusions. " /// "Furthermore, tumors with EML4-ALK fusions had significantly higher levels of ERCC1, a molecule with a key role in platinum drug efficacy, than tumors without EML4-ALK fusions."
EML4_ALK- 23559882renal cell carcinoma;non small cell lung cancer;colorectal cancer;small - - Those agents range from improved cytotoxics such as pemetrexed, to targeted therapies such as tyrosine kinase inhibitors of the epidermal growth factor receptor and agents that target the EML4-ALK gene mutation. /// "Those agents range from improved cytotoxics such as pemetrexed, to targeted therapies such as tyrosine kinase inhibitors of the epidermal growth factor receptor and agents that target the EML4-ALK gene mutation. "
EML4_ALK- 23098378adenocarcinoma - - In this series, 230 resected lung adenocarcinomas from smoker (>100 cigarettes in lifetime) at single center (Shanghai Cancer Center, Shanghai, China) were tested for mutation in EGFR, KRAS, BRAF, HER2, EML4-ALK and PIK3CA. /// "Among 230 smokers, we detected 100 (43.5%) EGFR mutations, 38 (16.5%) KRAS mutations, 8 (3.5%) PIK3CA mutations, 7 (3.0%) BRAF mutations and 7 (3.0%) EML4-ALK fusions. "
EML4_ALK- 22056890- - - Successful long-term treatment with pemetrexed of NSCLC associated with EML4-ALK and low thymidylate synthase expression. /// Successful long-term treatment with pemetrexed of NSCLC associated with EML4-ALK and low thymidylate synthase expression..
EML4_ALK- 25393796non small cell lung cancer;lung cancer - - This patient and another patient with EML4-ALK variant 3a/b initially responded sequentially to crizotinib and then alectinib, a next-generation ALK inhibitor, but developed acquired resistance to alectinib with the presence of a mutation in amino acid residue 1171 (I1171N and I1171S respectively) located in the hydrophobic regulatory spine (R-spine) of the ALK kinase in both the cases as identified by a comprehensive next-generation sequencing-based assay performed on biopsies of new liver metastases that developed during alectinib treatment. /// "This patient and another patient with EML4-ALK variant 3a/b initially responded sequentially to crizotinib and then alectinib, a next-generation ALK inhibitor, but developed acquired resistance to alectinib with the presence of a mutation in amino acid residue 1171 (I1171N and I1171S respectively) located in the hydrophobic regulatory spine (R-spine) of the ALK kinase in both the cases as identified by a comprehensive next-generation sequencing-based assay performed on biopsies of new liver metastases that developed during alectinib treatment."
EML4_ALK- 25612681non small cell lung cancer;lung cancer - - The discovery of driver oncogene alterations in non-small cell lung cancer (NSCLC), such as EGFR, EML4-ALK, MET and RAS, as well as the identification of their specific targeted inhibitors have led to new opportunities for treatment of this tumor. /// " The discovery of driver oncogene alterations in non-small cell lung cancer (NSCLC), such as EGFR, EML4-ALK, MET and RAS, as well as the identification of their specific targeted inhibitors have led to new opportunities for treatment of this tumor. "
EML4_ALK- 26107243non small cell lung cancer - - A Pooled Analysis on Crizotinib in Treating Chinese Patients with EML4-ALK Positive Non-small-cell Lung Cancer. /// This pooled analysis suggests that crizotinib based regimens are associated with good response rate and accepted toxicities in treating Chinese patients with EML4-ALK positive non-small-cell lung cancer.. /// Clinical studies evaluating the efficacy and safety of crizotinib based regimens on response and safety for Chinese patients with EML4-ALK positive non-small-cell lung cancer were identified by using a predefined search strategy. /// This analysis was conducted to evaluate the efficacy and safety of crizotinib based regimens in treating Chinese patients with EML4-ALK positive non-small-cell lung cancer. /// "In crizotinib based regimens, 3 clinical studies which including 128 Chinese patients with EML4-ALK positive non-small-cell lung cancer and treated with crizotinib based regimen were considered eligible for inclusion. " /// A Pooled Analysis on Crizotinib in Treating Chinese Patients with EML4-ALK Positive Non-small-cell Lung Cancer..
EML4_ALK- 24200637non small cell lung cancer;colorectal cancer;lung cancer - - A second NSCLC patient showed an EML4-ALK fusion with ALK, EGFR, and MET mutations. /// "A second NSCLC patient showed an EML4-ALK fusion with ALK, EGFR, and MET mutations. "
EML4_ALK- 22317764adenocarcinoma - - Two hundred and sixty-six (76.2%) tumors harbored EGFR mutations, 16 (4.6%) HER2 mutations, 15 (4.3%) EML4-ALK fusions, seven (2.0%) KRAS mutations, and two (0.6%) BRAF mutations. /// "Two hundred and sixty-six (76.2%) tumors harbored EGFR mutations, 16 (4.6%) HER2 mutations, 15 (4.3%) EML4-ALK fusions, seven (2.0%) KRAS mutations, and two (0.6%) BRAF mutations."
EML4_ALK- 24183104non small cell lung cancer;lung cancer;adenocarcinoma - - For lung cancer patients with positive brushing cytology, analysis of EGFR, K-ras and EML4-ALK fusions were carried out, utilizing reverse transcription-polymerase chain reaction and Sanger sequencing on the cell-derived RNA retrieved from waste brushing samples. /// "Of the 19 patients with adenocarcinoma or non-small cell lung cancer not otherwise specified harboring wild-type EGFR and K-ras, two cases (10.5%) were identified to harbor EML4-ALK fusions. "
EML4_ALK- 18166835squamous cell carcinoma - - Using reverse transcription-polymerase chain reaction for EML4-ALK fusion mRNA, we investigated 149 lung adenocarcinomas, 48 squamous cell carcinomas, 3 large-cell neuroendocrine carcinomas, and 21 small-cell carcinomas. /// "Using reverse transcription-polymerase chain reaction for EML4-ALK fusion mRNA, we investigated 149 lung adenocarcinomas, 48 squamous cell carcinomas, 3 large-cell neuroendocrine carcinomas, and 21 small-cell carcinomas." /// "Herein, we present results of a first large scale study of EML4-ALK fusion in lung cancers. " /// "Five of 149 adenocarcinomas (3.4%) showed EML4-ALK fusion mRNA, this being totally lacking in carcinomas of other types (0/72). " /// EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers.. /// The five fusion cases featured two EML4-ALK variant 1 fusions and three variant 2 fusions. /// "In the present first investigation of EML4-ALK fusion in a large study of lung cancers (5/221), we found an interesting histotype-genotype relationship. " /// Tumors featuring EML4-ALK fusion constitute one subtype of NSCLC that might be highly sensitive to ALK inhibitors. /// "Five of 149 adenocarcinomas (3.4%) showed EML4-ALK fusion mRNA, this being totally lacking in carcinomas of other types (0/72)."
EML4_ALK- 24913807mucinous carcinoma;non small cell lung cancer - - Using the direct RNA sequencing method, we discovered a rare CD74-NRG1 fusion (8 %), an echinoderm microtubule-associated protein like 4 (EML4)-ALK fusion (17 %), and three KRAS mutations (25 %).
EML4_ALK- 25806325anaplastic large cell lymphoma;non small cell lung cancer;lung cancer;ly - - In the last five years the interest for ALK small inhibitors grew rapidly, mainly because it was discovered that a small but significant percentage of non-small cell lung cancer (NSCLC) patients carries the oncogenic fusion protein EML4-ALK, in addition to about half percent of anaplastic large cell lymphoma (ALCL) patients, an aggressive but definitely rarer non Hodgkin's T cell lymphoma, and other malignancies. /// "In the last five years the interest for ALK small inhibitors grew rapidly, mainly because it was discovered that a small but significant percentage of non-small cell lung cancer (NSCLC) patients carries the oncogenic fusion protein EML4-ALK, in addition to about half percent of anaplastic large cell lymphoma (ALCL) patients, an aggressive but definitely rarer non Hodgkin's T cell lymphoma, and other malignancies. "
EML4_ALK- 22690483breast cancer;lung cancer;melanoma - - Examples are imatinib in CML and GIST, trastuzumab in HER2 positive breast cancer, gefitinib in mutated EGFR, crizotinib in EML4-ALK positive lung cancer and, also, vemurafenib in BRAF 600E mutated metastatic melanoma. /// "Examples are imatinib in CML and GIST, trastuzumab in HER2 positive breast cancer, gefitinib in mutated EGFR, crizotinib in EML4-ALK positive lung cancer and, also, vemurafenib in BRAF 600E mutated metastatic melanoma. "
EML4_ALK- 19383809lung cancer PCR - Immunohistochemical detection of EML4-ALK has proved difficult, however, likely as a result of low transcriptional activity conferred by the promoter-enhancer region of EML4. /// Our iAEP method discriminated between tumors positive or negative for EML4-ALK in a test set of specimens. /// The sensitivity of EML4-ALK detection by immunohistochemistry should be increased adequately. /// "These 8 tumors were found to include 1 with EML4-ALK variant 1, 1 with variant 2, 3 with variant 3, and 2 with previously unidentified variants (designated variants 6 and 7). " /// " EML4-ALK is a transforming fusion tyrosine kinase, several isoforms of which have been identified in lung cancer. "
EML4_ALK- 25971657lung cancer - - Constitutive dimerization of EML4-ALK mediated by a dimerization motif of EML4 results in kinase activation. /// The EML4-ALK oncogene: targeting an essential growth driver in human cancer. /// The EML4-ALK oncogene: targeting an essential growth driver in human cancer.. /// "By screening such a library of lung adenocarcinoma with a focus formation assay, we discovered the EML4-ALK fusion-type oncogene. "
EML4_ALK- 23415374adenocarcinoma - - The EML4-ALK transcript or CHFR hypermethylation was found in 11 (6.7%) or 16 (10%) adenocarcinomas, respectively, whereas EGFR or KRAS mutation was detected in 48 (29%) or 13 (8%) cases, respectively. /// "The EML4-ALK transcript or CHFR hypermethylation was found in 11 (6.7%) or 16 (10%) adenocarcinomas, respectively, whereas EGFR or KRAS mutation was detected in 48 (29%) or 13 (8%) cases, respectively." /// " Excluding epidermal growth factor receptor (EGFR) mutation, v-Ki-ras2/Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion, the genetic alterations involved in lung adenocarcinogenesis, especially those linked to poor clinical outcomes, are still unknown. "
EML4_ALK- 22483782non small cell lung cancer;lung cancer - - Twenty-eight (3.9%) patients harbored the EML4-ALK gene. /// Clinicoradiologic characteristics of patients with lung adenocarcinoma harboring EML4-ALK fusion oncogene. /// The clinicopathological characteristics of each patient were compared among the subgroups stratified by the EML4-ALK gene status. /// We explored the EML4-ALK gene in a relatively large cohort and reviewed the clinicoradiologic background of the patients. /// Clinicoradiologic characteristics of patients with lung adenocarcinoma harboring EML4-ALK fusion oncogene.. /// "Younger age (p=0.001), no or light history of smoking (p=0.05) and normal serum carcinoembryonic antigen (CEA) level (p=0.04) were characteristics of the patients with EML4-ALK." /// "Younger age (p=0.001), no or light history of smoking (p=0.05) and normal serum carcinoembryonic antigen (CEA) level (p=0.04) were characteristics of the patients with EML4-ALK. "
EML4_ALK- 22443647non small cell lung cancer;lung cancer - - The monoclonal antibody to EGFR, cetuximab, improves survival in patients with metastatic NSCLC, and the inhibitor of the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion protein, crizotinib, has resulted in an unprecedented overall survival advantage in patients harboring the EML4-ALK translocation. /// "The monoclonal antibody to EGFR, cetuximab, improves survival in patients with metastatic NSCLC, and the inhibitor of the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion protein, crizotinib, has resulted in an unprecedented overall survival advantage in patients harboring the EML4-ALK translocation. "
EML4_ALK- 23408463lung cancer;adenocarcinoma - - All informative pairs were concordant either for the norm (32 of 36 pairs) or for the presence of EML4-ALK gene fusion (4 of 36 pairs). /// RNA extraction followed by reverse transcriptase-polymerase chain reaction analysis for the EML4-ALK translocation was performed for 44 EGFR mutation-negative sample pairs. /// Detection of EGFR mutations and EML4-ALK rearrangements in lung adenocarcinomas using archived cytological slides..
EML4_ALK- 19386350non small cell lung cancer;squamous cell carcinoma;adenocarcinoma ISH - Recently, the fusion gene EML4-ALK was identified in non-small cell lung carcinoma, which could be a potential therapeutic target. /// Anaplastic lymphoma kinase immunohistochemistry may have utility as a screening tool or as a surrogate marker for the molecular techniques to detect the EML4-ALK fusion gene in these tumors.. /// "In conclusion, anaplastic lymphoma kinase immunoreactivity in non-small cell lung carcinomas was associated with transcriptional up-regulation, ALK locus rearrangement, and the presence of EML4-ALK fusion transcript. " /// The presence of EML4-ALK fusion transcript was confirmed in 2 cases by reverse transcriptase-polymerase chain reaction. /// Florescence in situ hybridization for the ALK locus and reverse transcriptase-polymerase chain reaction for EML4-ALK were performed on tumors positive for anaplastic lymphoma kinase by immunohistochemistry.
EML4_ALK- 26767032- ISH - Our data was apparently inconsistent with the traditional view that the EML4-ALK fusion gene in patients is resistant to EGFR-TKIs.. /// Two patients harboring both EGFR mutation and EML4-ALK rearrangement were detected in this study. /// "The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangement is almost in mutual exclusion to epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, with rare exceptions." /// " The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangement is almost in mutual exclusion to epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, with rare exceptions. "
EML4_ALK- 24496003non small cell lung cancer;squamous cell carcinoma;non small cell lung cancer;small cell lung canc - - Two ALK-rearranged NSCLC PDX models were identified: one carried a well-known EML4-ALK variant 3a/b and the other harbored a novel huntingtin interacting protein 1 (HIP1)-ALK fusion gene. /// "Screening of 99 lung cancer PDX models by the NanoString ALK fusion assay identified two ALK-rearranged non-small-cell lung cancer (NSCLC) tumors, including one harboring a previously known echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion and another containing an unknown ALK fusion variant. "
EML4_ALK- 22964709non small cell lung cancer;lung cancer ISH - Moreover, 2 patients with concurrent EML4-ALK and EGFR mutations had superior PFS after EGFR-TKI compared to patients with single EML4-ALK rearrangement. /// Patients with stage IV NSCLC were screened for EML4-ALK rearrangement and EGFR mutations at the Peking University Cancer Hospital. /// EML4-ALK rearrangement and its clinical significance in Chinese patients with advanced non-small cell lung cancer.. /// Response to EGFR-tyrosine kinase inhibitor (TKI) was similar between patients with EML4-ALK rearrangement and EGFR mutation (33.3 vs. /// EML4-ALK was identified using fluorescent in situ hybridization and confirmed by immunohistochemistry. /// Patients with EML4-ALK were more likely to present the EGFR wild type (WT. /// Patients with EML4-ALK conferred similar objective response rates after EGFR-TKI although inferior PFS compared to those with EGFR mutation. /// Coexistence of EML4-ALK and EGFR mutation might represent a separate NSCLC genotype.. /// The incidence of EML4-ALK was 9.7% (11/113). /// Patients with EML4-ALK were more likely to present the EGFR wild type (WT; p = 0.033).
EML4_ALK- 19667264non small cell lung cancer;lung cancer;adenocarcinoma ISH - EML4-ALK was identified by using fluorescent in situ hybridization for ALK rearrangements and was confirmed by immunohistochemistry for ALK expression. /// EML4-ALK defines a molecular subset of NSCLC with distinct clinical characteristics. /// "Of 141 tumors screened, 19 (13%) were EML4-ALK mutant, 31 (22%) were EGFR mutant, and 91 (65%) were wild type (WT/WT) for both ALK and EGFR. " /// "To aid in identification and treatment of these patients, we examined the clinical characteristics and treatment outcomes of patients who had NSCLC with and without EML4-ALK. " /// "Among patients with metastatic disease, EML4-ALK positivity was associated with resistance to EGFR tyrosine kinase inhibitors (TKIs). " /// "Compared with the EGFR mutant and WT/WT cohorts, patients with EML4-ALK mutant tumors were significantly younger (P < .001 and P = .005) and were more likely to be men (P = .036 and P = .039). " /// Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK.. /// Patients in the EML4-ALK cohort and the WT/WT cohort showed similar response rates to platinum-based combination chemotherapy and no difference in overall survival. /// "Eighteen of the 19 EML4-ALK tumors were adenocarcinomas, predominantly the signet ring cell subtype. " /// The EML4-ALK fusion oncogene represents a novel molecular target in a small subset of non-small-cell lung cancers (NSCLC).
EML4_ALK- 26327925non small cell lung cancer;lung cancer ISH - Fluorescence in situ hybridization is used as the diagnostic test for detecting an EML4-ALK rearrangement.
EML4_ALK- 24189654acute myeloid leukemia;myeloid leukemia;leukemia;melanoma - - In clinical samples with ? 10% tumor cells, UW-OncoPlex correctly identified 129 of 130 known mutations [sensitivity 99.2%, (95% CI, 95.8%-99.9%)], including single nucleotide variants, small insertions and deletions, internal tandem duplications, gene copy number gains and amplifications, gene copy losses, chromosomal gains and losses, and actionable genomic rearrangements, including ALK-EML4, ROS1, PML-RARA, and BCR-ABL.
EML4_ALK- 24885608non small cell lung cancer;lung cancer ISH - The discovery of the fusion gene echinodermmicro tubule associated proteinlike 4-anaplastic lymphoma kinase, EML4-ALK, in patients with non-small-cell lung cancer has led to the remarkable development of anaplastic lymphoma kinase inhibitors, such as crizotinib. /// " The discovery of the fusion gene echinodermmicro tubule associated proteinlike 4-anaplastic lymphoma kinase, EML4-ALK, in patients with non-small-cell lung cancer has led to the remarkable development of anaplastic lymphoma kinase inhibitors, such as crizotinib. "
EML4_ALK- 20009909non small cell lung cancer;lung cancer;adenocarcinoma ISH - At least seven ALK gene rearrangement variants have been described involving different EML4-ALK breakpoints or rarely other non-EML4 fusion partners. /// At least seven ALK gene rearrangement variants have been described involving different EML4-ALK breakpoints or rarely other non-EML4 fusion partners.
EML4_ALK- 18320074non small cell lung cancer;lung cancer;adenocarcinoma ISH - Because the EML4-ALK fusion was only shown by a reverse transcription-polymerase chain reaction approach, we developed fluorescent in situ hybridization assays to interrogate more than 600 NSCLCs using break-apart probes for EML4 and ALK. /// "We also observed that, in most cases in which an EML4/ALK alteration is detected, not all of the tumor cells harbor the lesion. " /// We found that EML4-ALK fusions occur in less than 3% of NSCLC samples and that EML4 and/or ALK amplifications also occur. /// EML4-ALK fusion lung cancer: a rare acquired event..
EML4_ALK- 23900599pulmonary cancer - - epidermal growth factor receptor (EGFR) mutations and EML4-ALK translocations and will certainly lead to a variety of novel predictive markers not only for pulmonary adenocarcinoma but also for other pulmonary neoplasms.
EML4_ALK- 24423920breast carcinoma - - (4) no EGFR, Kras mutations or EML4-ALK translocations were found, but PI3K and Braf mutations were observed in 26% of cases. /// "Tissue sections of 138 TNBCs were used (1) to compare EGFR amplification and expression by silver in situ hybridisation (SISH) to qPCR and immunohistochemistry (IHC) and (2) to search for EGFR mutations, along with Kras, PI3K, Braf and HER-2 mutations and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) translocation. "
EML4_ALK- 25582278lung cancer;adenocarcinoma - - EGFR/KRAS mutations and EML4-ALK fusions were similar between GGO and solid adenocarcinomas. /// "It is important that we understand GGO lesions of lung adenocarcinoma to identify molecular biomarkers including EGFR, KRAS and EML4-ALK. " /// "EGFR, KRAS and EML4-ALK mutations were detected by qPCR. "
EML4_ALK- 24123310non small cell lung cancer - - The aim of our study was to investigate novel mutations of Eph genes (EPHA1-8, EPHB1-4, EPHB6) and their association with clinically relevant mutations in BRAF, EML4-ALK, EGFR, INSR, KDR, KRAS, MET, PDGFRA, PDGFRB, PIK3, PTEN, RET, and TP53 in NSCLC patients.
EML4_ALK- 23617234lung cancer;adenocarcinoma - - To our knowledge, this is the first report of synchronous, bilateral lung adenocarcinomas composed of EML4-ALK positive and negative ones.. /// A case of synchronous bilateral lung cancers: EML4-ALK positive adenocarcinoma in the right lung and adenocarcinoma in situ (the former bronchioloalveolar carcinoma) in the left lung. /// "The woman had EML4-ALK positive lung adenocarcinoma in the right lower lung while adenocarcinoma in situ in the left upper lung, which was EML4-ALK negative. " /// A case of synchronous bilateral lung cancers: EML4-ALK positive adenocarcinoma in the right lung and adenocarcinoma in situ (the former bronchioloalveolar carcinoma) in the left lung.. /// Reported herein is a case of synchronous EML4-ALK positive lung adenocarcinoma and adenocarcinoma in situ in the bilateral lungs of a 55-year-old Japanese woman. /// "To our knowledge, this is the first report of synchronous, bilateral lung adenocarcinomas composed of EML4-ALK positive and negative ones.. "

ChimerSEQ

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The fusion gene pair EML4--ALK information is available in CHIMERSEQ (CHIMERDB 3.0) database.

Fusion_pair5'Gene Junction (Chr/Position/Strand)3'Gene Junction (Chr/Position/Strand)5'Gene_locus3'Gene_locusBreakpoint_TypeGenome_BuildFrameChr_infoCancertype_or_diseaseBarcodeIDGene TypeSource
EML4_ALKchr2/42491871/+ chr2/29446394/- 2p21 2p23.2 Exonic hg19 In-Frame Intra-chr LUAD TCGA-67-6215-01A Oncogene; FusionScan
EML4_ALKchr2/42522656/+ chr2/29446394/- 2p21 2p23.2 Exonic hg19 In-Frame Intra-chr LUAD TCGA-78-7163-01A Oncogene; FusionScan
EML4_ALKchr2/42492090/+ chr2/29446393/- 2p21 2p23.2 Exonic hg19 Out-of-Frame Intra-chr LUAD TCGA-50-8460-01A Oncogene; TopHat-Fusion
EML4_ALKchr2/42492090/+ chr2/29446393/- 2p21 2p23.2 Exonic hg19 Out-of-Frame Intra-chr LUAD TCGA-67-6216-01A Oncogene; TopHat-Fusion
EML4_ALKchr2/42491870/+ chr2/29446393/- 2p21 2p23.2 Exonic hg19 In-Frame Intra-chr LUAD TCGA-67-6216-01A Oncogene; TopHat-Fusion
EML4_ALKchr2/42491870/+ chr2/29446393/- 2p21 2p23.2 Exonic hg19 In-Frame Intra-chr LUAD TCGA-67-6215-01A Oncogene; TopHat-Fusion
EML4_ALKchr2/42522655/+ chr2/29446393/- 2p21 2p23.2 Exonic hg19 In-Frame Intra-chr LUAD TCGA-78-7163-01A Oncogene; TopHat-Fusion
EML4_ALKchr2/42483770/ chr2/29416090/ 2p21 2p23.2 Exonic hg19 - Intra-chr NA JQ828841 Oncogene; ChiTaRs
EML4_ALKchr2/42552694/ chr2/29415644/ 2p21 2p23.2 Exonic hg19 - Intra-chr NA AB275889 Oncogene; ChiTaRs
EML4_ALKchr2/42492091/ chr2/29416090/ 2p21 2p23.2 Exonic hg19 - Intra-chr NA EU236948 Oncogene; ChiTaRs
EML4_ALKchr2/42522657/ chr2/29416042/ 2p21 2p23.2 Exonic hg19 - Intra-chr NA AB462411 Oncogene; ChiTaRs
EML4_ALKchr2/42528532/ chr2/29416041/ 2p21 2p23.2 Exonic hg19 - Intra-chr NA AB462412 Oncogene; ChiTaRs
EML4_ALKchr2/42531692/ chr2/29446319/ 2p21 2p23.2 Exonic hg19 - Intra-chr NA GU797894 Oncogene; ChiTaRs
EML4_ALKchr2/42532902/ chr2/29446319/ 2p21 2p23.2 Exonic hg19 - Intra-chr NA GU797895 Oncogene; ChiTaRs
EML4_ALKchr2/42492091/+ chr2/29446394/- 2p21 2p23.2 Exonic hg19 In-frame Intra-chr LUAD TCGA-50-8460-01A Oncogene; PRADA
EML4_ALKchr2/42491871/+ chr2/29446394/- 2p21 2p23.2 Exonic hg19 In-frame Intra-chr LUAD TCGA-67-6215-01A Oncogene; PRADA
EML4_ALKchr2/42492091/+ chr2/29446394/- 2p21 2p23.2 Exonic hg19 In-frame Intra-chr LUAD TCGA-67-6216-01A Oncogene; PRADA
EML4_ALKchr2/42522656/+ chr2/29446394/- 2p21 2p23.2 Exonic hg19 In-frame Intra-chr LUAD TCGA-78-7163-01A Oncogene; PRADA
EML4_ALKchr2/42552694/+ chr2/29446394/- 2p21 2p23.2 Exonic hg19 In-frame Intra-chr LUAD TCGA-86-A4P8-01A Oncogene; PRADA
EML4_ALKchr2/42492091/+ chr2/29449940/- 2p21 2p23.2 Exonic hg19 In-frame Intra-chr THCA TCGA-E8-A432-01A Oncogene; PRADA
EML4_ALKchr2/42522660/ chr2/29415644/ 2p21 2p23.2 Exonic hg19 - Intra-chr acute lymphoblastic leukemia;chronic lymphocytic leukemia;Follicular lymphoma;diffuse large B cell lymphoma;Peripheral T cell lymphoma;Hodgkin disease;adenocarcinoma;adenosquamous carcinoma;squamous cell carcinoma;Nonneoplastic hematologic disorder/lesion;Nonneoplastic epithelial disorder/lesion;non small cell lung cancer AB274722 Oncogene; ChiTaRs

ChiTaRS 2.1

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The fusion gene pair EML4--ALK information is available in CHITARS database.

OrganismChimeraIDFusion genepairHead geneTail gene
GeneChromosomeGenomic_startGenomic_stopStrandFusiongene_startposFusiongene_endpos%IdentGeneChromosomeGenomic_startGenomic_stopStrandFusiongene_startposFusiongene_endpos%Ident
Human JQ828841EML4--ALK EML42 42396752 42483770 + 1 338 100 ALK2 29416090 29446449 - 337 2082 99.9
Human AB275889EML4--ALK EML42 42396483 42552694 + 2 2512 99.9 ALK2 29415644 29446394 - 2513 4653 99.7
Human EU236948EML4--ALK EML42 42396752 42492091 + 1 700 100 ALK2 29416090 29446396 - 699 2391 100
Human AB274722EML4--ALK EML42 42396483 42522660 + 2 1764 99.8 ALK2 29415644 29446396 - 1758 3900 99.7
Human AB462411EML4--ALK EML42 42396685 42522657 + 2 1558 99.9 ALK2 29416042 29446465 - 1556 3365 99.8
Human AB462412EML4--ALK EML42 42396685 42528532 + 2 1709 99.9 ALK2 29416041 29446382 - 1708 3435 99.9
Human GU797894EML4--ALK EML42 42531627 42531692 + 1 66 100 ALK2 29446319 29446427 - 63 171 100
Human GU797895EML4--ALK EML42 42531627 42532902 + 1 126 100 ALK2 29446319 29446432 - 123 236 100

FARE-CAFE

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The fusion gene pair EML4--ALK information is available in FARE-CAFE.

Cancer Information
Fusion_ProteinCancer_TypeFP_Experimental_MethodFP_KaryotypeFP_Reference
EML4-ALK Lung cancer RT–PCR (2)(p21;p23) PubMed:17625570

Genomic Information
Fusion_ProteinFusion_Protein_Isoforms5'_ProteinF_B_PFBP_in_Exon/Intron5'_Protein_on_Positive/Negative_Strands3'_ProteinS_B_P3'_Protein_on_Positive/Negative_StrandsSBP_in_Exon/IntronFusion_Protein_mRNA_sequenceFusion_Protein_ReferenceFusion_Protein_GenbankID
EML4-ALK EML4-ALK-Isoform1 EML4 42552694 0 1 ALK 29446347 0 1 ATATAATGTCTAACTCGGGAGACTATGAAATATTGTACTtgtaccgccggaagcaccaggagctgcaagccatgcagatggagctgc 17625570 _
EML4-ALK EML4-ALK-Isoform10 EML4 _ _ 1 ALK _ 0 _ tggagtgagaCtcctctgat 19737969 _
EML4-ALK EML4-ALK-Isoform11 EML4 _ _ 1 ALK _ 0 _ tggtatcttcCagacaccaa 19737969 _
EML4-ALK EML4-ALK-Isoform2 EML4 42522660 0 1 ALK 29446345 0 1 CTACTGTAGAGCCCACACCTGGGAAAGGACCTAAAGtGTACcgccggaagcaccaggagctgcaagccatgcagatggagctgcag 17625570 _
EML4-ALK EML4-ALK-Isoform3 EML4 42492091 0 1 ALK 29446375 0 1 tcgcgaaaaaaacagccaagTgtaccgccggaagcaccag 18083107 _
EML4-ALK EML4-ALK-Isoform4 EML4 _ _ 1 ALK 29446369 0 1 catcatcaaccaagTgtaccgccggaagcaccaggagctg 18593892 _
EML4-ALK EML4-ALK-Isoform5 EML4 _ _ 1 ALK _ 0 _ cgcgaaaaaaacagccaagTgtaccgccggaa 18593892 _
EML4-ALK EML4-ALK-Isoform6 EML4 _ _ 1 ALK _ 0 _ ctgaaagagaaatagagCaccaggagc 19383809 _
EML4-ALK EML4-ALK-Isoform7 EML4 _ _ 1 ALK _ 0 _ acctggtaacAcaattttgt 19737969 _
EML4-ALK EML4-ALK-Isoform8 EML4 _ _ 1 ALK _ 0 _ ataaactcatGtgttggggg 19737969 _
EML4-ALK EML4-ALK-Isoform9 EML4 _ _ 1 ALK _ 0 _ tatgatagatCacattggta 19737969 _

Domains and DDI Information
Fusion_ProteinFusion_Protein_IsoformsDomains_in_5'PartnerDDIs_for_Domains_in_5'PartnerDomains_in_3'PartnerDDIs_for_Domains_in_3'Partner5'_Protein5'P_Domains5'P_Domains_DDI_partners3'_Protein3'P_Domains3'P_Domains_DDI_partnersMissing_FP_DomainsMissing_FP_Domains_DDI
EML4-ALK EML4-ALK-Isoform1 1) WD40
1) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
1) MAM
2) Gly_rich
1) ig , Astacin , MATH
EML4 1) HELP
2) WD40
1) WD40
2) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
ALK 1) MAM
2) Gly_rich
3) Pkinase_Tyr
1) ig , Astacin , MATH
2) Inhibitor_Mig-6 , Y_phosphatase , Pkinase_Tyr , SH3_9 , EphA2_TM , CH , SH3_1 , Pkinase , BPS , AvrPto , FERM_M , SH2
- -
EML4-ALK EML4-ALK-Isoform10 - - - -EML4 1) HELP
2) WD40
1) WD40
2) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
ALK 1) MAM
2) Gly_rich
3) Pkinase_Tyr
1) ig , Astacin , MATH
2) Inhibitor_Mig-6 , Y_phosphatase , Pkinase_Tyr , SH3_9 , EphA2_TM , CH , SH3_1 , Pkinase , BPS , AvrPto , FERM_M , SH2
1) HELP
2) WD40
3) MAM
4) Gly_rich
5) Pkinase_Tyr
1) WD40
2) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
3) ig , Astacin , MATH
4) Inhibitor_Mig-6 , Y_phosphatase , Pkinase_Tyr , SH3_9 , EphA2_TM , CH , SH3_1 , Pkinase , BPS , AvrPto , FERM_M , SH2
EML4-ALK EML4-ALK-Isoform11 - - - -EML4 1) HELP
2) WD40
1) WD40
2) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
ALK 1) MAM
2) Gly_rich
3) Pkinase_Tyr
1) ig , Astacin , MATH
2) Inhibitor_Mig-6 , Y_phosphatase , Pkinase_Tyr , SH3_9 , EphA2_TM , CH , SH3_1 , Pkinase , BPS , AvrPto , FERM_M , SH2
1) HELP
2) WD40
3) MAM
4) Gly_rich
5) Pkinase_Tyr
1) WD40
2) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
3) ig , Astacin , MATH
4) Inhibitor_Mig-6 , Y_phosphatase , Pkinase_Tyr , SH3_9 , EphA2_TM , CH , SH3_1 , Pkinase , BPS , AvrPto , FERM_M , SH2
EML4-ALK EML4-ALK-Isoform2 1) WD40
1) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
1) MAM
2) Gly_rich
1) ig , Astacin , MATH
EML4 1) HELP
2) WD40
1) WD40
2) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
ALK 1) MAM
2) Gly_rich
3) Pkinase_Tyr
1) ig , Astacin , MATH
2) Inhibitor_Mig-6 , Y_phosphatase , Pkinase_Tyr , SH3_9 , EphA2_TM , CH , SH3_1 , Pkinase , BPS , AvrPto , FERM_M , SH2
- -
EML4-ALK EML4-ALK-Isoform3 1) WD40
1) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
1) MAM
2) Gly_rich
1) ig , Astacin , MATH
EML4 1) HELP
2) WD40
1) WD40
2) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
ALK 1) MAM
2) Gly_rich
3) Pkinase_Tyr
1) ig , Astacin , MATH
2) Inhibitor_Mig-6 , Y_phosphatase , Pkinase_Tyr , SH3_9 , EphA2_TM , CH , SH3_1 , Pkinase , BPS , AvrPto , FERM_M , SH2
- -
EML4-ALK EML4-ALK-Isoform4 - - 1) MAM
2) Gly_rich
1) ig , Astacin , MATH
EML4 1) HELP
2) WD40
1) WD40
2) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
ALK 1) MAM
2) Gly_rich
3) Pkinase_Tyr
1) ig , Astacin , MATH
2) Inhibitor_Mig-6 , Y_phosphatase , Pkinase_Tyr , SH3_9 , EphA2_TM , CH , SH3_1 , Pkinase , BPS , AvrPto , FERM_M , SH2
1) HELP
2) WD40
1) WD40
2) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
EML4-ALK EML4-ALK-Isoform5 - - - -EML4 1) HELP
2) WD40
1) WD40
2) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
ALK 1) MAM
2) Gly_rich
3) Pkinase_Tyr
1) ig , Astacin , MATH
2) Inhibitor_Mig-6 , Y_phosphatase , Pkinase_Tyr , SH3_9 , EphA2_TM , CH , SH3_1 , Pkinase , BPS , AvrPto , FERM_M , SH2
1) HELP
2) WD40
3) MAM
4) Gly_rich
5) Pkinase_Tyr
1) WD40
2) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
3) ig , Astacin , MATH
4) Inhibitor_Mig-6 , Y_phosphatase , Pkinase_Tyr , SH3_9 , EphA2_TM , CH , SH3_1 , Pkinase , BPS , AvrPto , FERM_M , SH2
EML4-ALK EML4-ALK-Isoform6 - - - -EML4 1) HELP
2) WD40
1) WD40
2) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
ALK 1) MAM
2) Gly_rich
3) Pkinase_Tyr
1) ig , Astacin , MATH
2) Inhibitor_Mig-6 , Y_phosphatase , Pkinase_Tyr , SH3_9 , EphA2_TM , CH , SH3_1 , Pkinase , BPS , AvrPto , FERM_M , SH2
1) HELP
2) WD40
3) MAM
4) Gly_rich
5) Pkinase_Tyr
1) WD40
2) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
3) ig , Astacin , MATH
4) Inhibitor_Mig-6 , Y_phosphatase , Pkinase_Tyr , SH3_9 , EphA2_TM , CH , SH3_1 , Pkinase , BPS , AvrPto , FERM_M , SH2
EML4-ALK EML4-ALK-Isoform7 - - - -EML4 1) HELP
2) WD40
1) WD40
2) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
ALK 1) MAM
2) Gly_rich
3) Pkinase_Tyr
1) ig , Astacin , MATH
2) Inhibitor_Mig-6 , Y_phosphatase , Pkinase_Tyr , SH3_9 , EphA2_TM , CH , SH3_1 , Pkinase , BPS , AvrPto , FERM_M , SH2
1) HELP
2) WD40
3) MAM
4) Gly_rich
5) Pkinase_Tyr
1) WD40
2) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
3) ig , Astacin , MATH
4) Inhibitor_Mig-6 , Y_phosphatase , Pkinase_Tyr , SH3_9 , EphA2_TM , CH , SH3_1 , Pkinase , BPS , AvrPto , FERM_M , SH2
EML4-ALK EML4-ALK-Isoform8 - - - -EML4 1) HELP
2) WD40
1) WD40
2) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
ALK 1) MAM
2) Gly_rich
3) Pkinase_Tyr
1) ig , Astacin , MATH
2) Inhibitor_Mig-6 , Y_phosphatase , Pkinase_Tyr , SH3_9 , EphA2_TM , CH , SH3_1 , Pkinase , BPS , AvrPto , FERM_M , SH2
1) HELP
2) WD40
3) MAM
4) Gly_rich
5) Pkinase_Tyr
1) WD40
2) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
3) ig , Astacin , MATH
4) Inhibitor_Mig-6 , Y_phosphatase , Pkinase_Tyr , SH3_9 , EphA2_TM , CH , SH3_1 , Pkinase , BPS , AvrPto , FERM_M , SH2
EML4-ALK EML4-ALK-Isoform9 - - - -EML4 1) HELP
2) WD40
1) WD40
2) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
ALK 1) MAM
2) Gly_rich
3) Pkinase_Tyr
1) ig , Astacin , MATH
2) Inhibitor_Mig-6 , Y_phosphatase , Pkinase_Tyr , SH3_9 , EphA2_TM , CH , SH3_1 , Pkinase , BPS , AvrPto , FERM_M , SH2
1) HELP
2) WD40
3) MAM
4) Gly_rich
5) Pkinase_Tyr
1) WD40
2) Acetyltransf_10 , CPSF_A , DUF1899 , IRK , ARPC4 , EZH2_WD-Binding , PH , Sec16_C , RGS , Cytochrom_C , G-gamma , eIF2A , Sec16 , Nup96 , Phosducin , MMS1_N , DUF1899 , DUF1900 , CAF1C_H4-bd , DEP , Methyltransf_4 , G-alpha , G-gamma , HELP , Lipase_GDSL_2 , Nucleopor_Nup85 , PI3_PI4_kinase , Ribosomal_S17e , P16-Arc , Mad3_BUB1_II , CPSF_A , HORMA , V-set , WD40 , PRMT5 , Ribosomal_S9
3) ig , Astacin , MATH
4) Inhibitor_Mig-6 , Y_phosphatase , Pkinase_Tyr , SH3_9 , EphA2_TM , CH , SH3_1 , Pkinase , BPS , AvrPto , FERM_M , SH2

miRNA Information
Fusion_ProteinmiRNAs_Targets_Fusion_proteinMissing_MiRNAs_Targets_Fusion_proteinFP_miRNA_Validation_method
EML4-ALK hsa-miR-132-3p hsa-miR-1hsa-miR-155-5phsa-miR-30b-5phsa-miR-16-5phsa-miR-877-3phsa-miR-652-3phsa-miR-148b-3p Microarray

Transcription Factors Information
Fusion_Protein5'P_Ref_mRNA_seqIDFP_Transcription_factorsFP_Missing_TFsFP_TF_Reference
EML4-ALK NM_001145076.1 - 1) TRIM28_HUMAN
2) MITF_HUMAN
3) STAT1_HUMAN
4) RBL2_HUMAN
5) P53_HUMAN
6) RUNX1_HUMAN
7) PRDM14_HUMAN
8) ESTROGEN RECEPTOR ALPHA_HUMAN
9) EGR1_HUMAN
10) FOS_HUMAN
11) GATA3_HUMAN
12) E2F1_HUMAN
13) SOX2_HUMAN
14) CTCF_HUMAN
15) BRG1_HUMAN
16) HNF4A_HUMAN
17) TFAP2C_HUMAN
18) FOXA1_HUMAN
19) ESR1_HUMAN
20) NR1H3_HUMAN
21) SETDB1_HUMAN
-

TicDB

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The fusion gene pair EML4--ALK information is available in TICDB.
HeadGeneTailGenePubmedIDSequence
EML4 ALK 17625570 ATATAATGTCTAACTCGGGAGACTATGAAATATTGTACTtgtaccgccggaagcaccaggagctgcaagccatgcagatggagctgc
EML4 ALK 17625570 CTACTGTAGAGCCCACACCTGGGAAAGGACCTAAAGtGTACcgccggaagcaccaggagctgcaagccatgcagatggagctgcag
EML4 ALK 18083107 tcgcgaaaaaaacagccaagTgtaccgccggaagcaccag
EML4 ALK 18593892 catcatcaaccaagTgtaccgccggaagcaccaggagctg
EML4 ALK 18593892 cgcgaaaaaaacagccaagTgtaccgccggaa
EML4 ALK 19383809 ctgaaagagaaatagagCaccaggagc
EML4 ALK 19737969 acctggtaacAcaattttgt
EML4 ALK 19737969 ataaactcatGtgttggggg
EML4 ALK 19737969 tatgatagatCacattggta
EML4 ALK 19737969 tggagtgagaCtcctctgat
EML4 ALK 19737969 tggtatcttcCagacaccaa

TUMOR FUSION Gene Data Portal

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The fusion gene pair EML4--ALK information is available in TUMOR FUSION Gene Data Portal.
CancerTCGA_barcodeFusionPairEvalue5'Gene_Junction3'Gene_JunctionTierFrameTNWGS_validation
KIRP 2Z-A9JJ-01A EML4__ALK 0.35 2:42472827/1 2:29446394/-1 tier1 In-frame 5558 NA
LUAD 50-8460-01A EML4__ALK 0.35 2:42492091/1 2:29446394/-1 tier1 In-frame 5559 NA
LUAD 67-6215-01A EML4__ALK 0.35 2:42491871/1 2:29446394/-1 tier1 In-frame 5560 validated
LUAD 67-6216-01A EML4__ALK 0.35 2:42492091/1 2:29446394/-1 tier1 In-frame 5561 NA
LUAD 78-7163-01A EML4__ALK 0.35 2:42522656/1 2:29446394/-1 tier2 In-frame 5562 NA
LUAD 86-A4P8-01A EML4__ALK 0.35 2:42552694/1 2:29446394/-1 tier3 In-frame 5563 NA
THCA E8-A432-01A EML4__ALK 0.35 2:42492091/1 2:29449940/-1 tier1 In-frame 5564 NA

FusionCancer

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The fusion gene pair EML4--ALK information is available in FusionCancer Database.
Database_IDHead_gene_symbolHead_breakpoint_locationTail_gene_symbolTail_breakpoint_locationCancer_typeSRA
FUSC003229EML4chr2:42522655ALKchr2:29415639Lung cancerERR164608
FUSC003229EML4chr2:42522656ALKchr2:29446394Lung cancerERR164608
FUSC003229EML4chr2:42552693ALKchr2:29415639Lung Cancer Non-Small CellSRR396804
FUSC003229EML4chr2:42552694ALKchr2:29446394Lung Cancer Non-Small CellSRR396804

ConjoinG

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The fusion gene pair EML4--ALK information is not available in ConjoinG Database.

1000Genome

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Fusion gene EML4--ALK has not been seen in a healthy sample (RNA-seq data from some samples from 1000 genomes project: Greger et al., Tandem RNA Chimeras Contribute to Transcriptome Diversity in Human Population and Are Associated with Intronic Genetic Variants, Plos One, Aug 2014 ). Therefore this candidate fusion gene has a low probability of being a false positive. [Fusion gene List compiled from FusionCatcher]

18Cancers

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Fusion gene EML4--ALK is found in a RNA-seq dataset of 18 types of cancers from 600 tumor samples (B. Alaei-Mahabadia et al., Global analysis of somatic structural genomic alterations and their impact on gene expression in diverse human cancers, PNAS, Nov. 2016)

Bodymap2

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Fusion gene EML4--ALK is not found in the list of known false positive fusion genes. The list has been generated from healthy human samples collected from 16 organs from Illumina BodyMap2 RNA-seq database. A candidate fusion gene found in this list has a very high probability of being a false positive. [Fusion gene List compiled from FusionCatcher]

HPA

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Fusion gene EML4--ALK is not found in a healthy sample (RNA-seq database of 27 healthy tissues from 95 human individuals). A candidate fusion gene found in this dataset has a very high probability of being a false positive. [Fusion gene List compiled from FusionCatcher]

Non_Tumor_Cells

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Fusion gene EML4--ALK was not found among the fusion genes which have been previously reported/found in non-tumor cell lines, like for example HEK293. The genes which are observed in those list can be considered as non-somatic mutation. [Fusion gene List compiled from FusionCatcher]

Babiceanu_Dataset

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The fusion gene pair EML4--ALK information is not available in Babiceanu_Dataset.

Banned_Dataset

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Fusion gene EML4--ALK is not found in the list of known false positive fusion genes. A candidate fusion gene found in this list has a very high probability of being a false positive. [Fusion gene List compiled from FusionCatcher]

Known_Fusions

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Fusion gene EML4--ALK has not been found in the list of fusions previously reported or published in scientific articles/reports/books/abstracts/databases, indexed by Google, Google Scholar, PubMed, etc. The list has been manually curated by FusionCatcher software. This label has only the role to answer with YES or NO the question "has ever before a given (candidate) fusion gene been published or reported?". This label does not have in anyway the role to provide the original references to the original scientific articles/reports/books/abstracts/databases for a given fusion gene.[Fusion gene List compiled from FusionCatcher]

ONGene Database

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The head gene EML4 is a known oncogene according to ONGENE database.


The tail gene ALK is a known oncogene according to ONGENE database.

Bushman Cancer Gene Database

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The head gene EML4 is cancer associated according to Bushman Cancer Gene database.


The tail gene ALK is cancer associated according to Bushman Cancer Gene database.

Tumor Gene Set By Uniprot

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The head gene EML4 is not a proto-oncogene or tumor suppresor gene according to Uniprot database.


The tail gene ALK is proto-oncogene or tumor suppresor gene according to Uniprot database.

Oesophagus_Dataset

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Fusion gene EML4--ALK is not found in oesophageal tumors from TCGA samples, which are published here.

Gliomas_Dataset

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Fusion gene EML4--ALK is not found in the RNA-seq dataset of 272 glioblastomas, published here.

Prostate_Dataset

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The fusion gene pair EML4--ALK information is not available in Prostate Dataset (150 prostate tumor RNAs, Robison et al, Integrative Clinical Genomics of Advanced Prostate Cancer, Cell, Vol. 161, May 2015, http://dx.doi.org/10.1016/j.cell.2015.05.001).

Pancreases_Dataset

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Fusion gene EML4--ALK is not found in pancreatic tumor dataset, published here.

GTEx

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Fusion gene EML4--ALK has not been found in a healthy sample (GTEx database of healthy tissues (thru FusionAnnotator)). A candidate fusion gene found in this set has a very high probability of being a false positive. [Fusion gene List compiled from FusionCatcher]

Klijin_Dataset

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The fusion gene pair EML4--ALK information is available in Klijn Dataset.

Cell lineGene 5'Gene 3'Read evidenceKinaseChromosome 5'Position 5'Chromosome 3'Position 3'Fusion type DNAFusion type RNAFusion protein lengthTissueKnown Fusion
NCI-H2228EML4ALK17Y242491871229446394InversioninFrame785LungFull fusion known

Fimereli_Dataset

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The fusion gene pair EML4--ALK information is not found in Fimereli_Dataset.

Literature

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The fusion gene pair EML4--ALK is found in known fusion genelist compiled from literature.

FusionGeneArticleLink
EML4--ALKDevelopment and Verification of an RNA Sequencing (RNA-Seq) Assay for the Detection of Gene Fusions in Tumorshttps://doi.org/10.1016/j.jmoldx.2018.03.007

Cortex_Dataset

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Fusion gene EML4--ALK is not found in Cortex_Dataset (Fusion genes found in healthy human brains (BA9 prefrontal cortex)) . A candidate fusion gene found in this dataset has a very high probability of being a false positive.

ChromothripsisDB

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The fusion gene pair EML4--ALK information is not available in ChromothripsisDB database.