NUT--BRD4

Hyperlinks to databases below
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

Link to Genecards:

NUT BRD4

COSMIC

The fusion gene pair NUT--BRD4 information is not available in COSMIC database.

ChimerKB

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The fusion gene pair NUT--BRD4 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
NUT_BRD4-/0/ -/0/ Exonic hg18 - - - - TICdb

ChimerPUB

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The fusion gene pair NUT--BRD4 information is available in CHIMERPUB (CHIMERDB 3.0) database.

Fusion_pairTranslocationPMIDDiseaseValidationGene TypeSentence_highlight
NUT_BRD4t(15;19) / t(15;19) / 16542442ewing sarcoma;sarcoma FISH;PCR - Pathological, cytogenetic, FISH and PCR analysis revealed a glycogenated carcinoma rarely expressing cytokeratins and showing t(15;19) and BRD4-NUT gene rearrangement. /// Midline carcinoma with t(15;19) and BRD4-NUT fusion oncogene in a 30-year-old female with response to docetaxel and radiotherapy.. /// The t(15;19) results in the fusion oncogene BRD4-NUT. /// "We herein describe, in detail, the laboratory methods by which the BRD4-NUT -rearrangement can be detected.. "
NUT_BRD4t(15;19) / 24655834- FISH - Cytogenetic and fluorescence in situ hybridization analyses revealed a t(15;19) and BRD4-NUT gene rearrangement. /// "In approximately two-thirds of cases, the characteristic t(15;19) results in the fusion oncogene BRD4-NUT. "
NUT_BRD4- 20034986- FISH - BRD4-NUT gene fusion was demonstrated by fluorescence in situ hybridization, confirming the diagnosis of NMC.
NUT_BRD4t(15;19) / 15483023- FISH - A balanced chromosomal translocation, t(15;19), resulting in the BRD4-NUT oncogene, has been identified in a lethal carcinoma of young people, a disease described primarily in case reports. /// "Eleven tumors had NUT gene rearrangements, including eight with BRD4-NUT fusions and three with novel rearrangements, which were designated as NUT variant. " /// "NRCs arise from midline structures in young people, and NRCs with BRD4-NUT are highly lethal, despite intensive therapies. " /// "In this first description of NUT-variant carcinomas, the average survival (96 weeks, n = 3) was longer than for BRD4-NUT carcinomas (28 weeks, n = 8). " /// NUT-variant carcinomas might have a less fulminant clinical course than those with BRD4-NUT fusions.
NUT_BRD4t(15;19) / t(15;19) / 22425924thymic carcinoma FISH - These tumors are characterized byrearrangement of the NUT (nuclear protein in testis) gene on chromosome 15q14, which in most cases fuses to the bromodomain containing 4 (BRD4) gene on chromosome 19 p13.1 through reciprocal t(15;19) translocation, resulting in constitutive BRD4-NUTfusion protein expression.
NUT_BRD4- 25675182pleural effusion FISH;PCR;RT-PCR - Dual-color split-apart fluorescence in situ hybridization (FISH) or reverse transcription polymerase chain reaction (RT-PCR) can be used to characterize the fusion gene, whether BRD4-NUT or BRD3-NUT, or NUT-variant.
NUT_BRD4t(15;19) / 26402248- FISH - Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare cancer that displays a characteristic chromosomal rearrangement of BRD4-NUT t(15;19)(q14;q13.1). /// Tumor cells demonstrated BRD4-NUT fusion on fluorescence in situ hybridization.
NUT_BRD4t(15;19) / 26001144- FISH - Eight cases had a fluorescence in situ hybridization-proven BRD4-NUT or BRD3-NUT rearrangement.
NUT_BRD4t(15;19) / 24457244squamous cell carcinoma FISH - Immunohistochemical staining for NUT was positive, and dual-color break-apart fluorescence in situ hybridization demonstrated BRD4-NUT rearrangement, thereby confirming a diagnosis of NMC. /// "The resultant BRD4-NUT fusion oncogene leads to global hypoacetylation and transcriptional repression of genes required for differentiation."" Although it was first reported in 1991 by Kubonishi et al., awareness of this condition remains low and the diagnosis is overlooked initially in a number of patients. "
NUT_BRD4- 19363441dysgerminoma FISH - In both instances, these tumors contained cryptic BRD4-NUT rearrangements, as confirmed by FISH using a refined set of probes. /// "Two new cases of NMC containing BRD4-NUT fusions were detected by C52 IHC, but missed by conventional FISH. "
NUT_BRD4- 22033856- FISH - The tumor is characterized by a rearrangement on the nuclear protein in testis (NUT) gene, located on chromosome 15q14, resulting in the BRD4-NUT fusion oncogene.
NUT_BRD419p13.1 / 20352379- - - These tumors are defined by rearrangement of the nuclear protein in testis (NUT) gene on chromosome 15q14, most commonly in a balanced translocation with the BRD4 gene on chromosome 19p13.1, resulting in the characteristic BRD4-NUT fusion gene and protein which blocks epithelial differentiation through chromatin binding.
NUT_BRD419p13.1 / 18552174- PCR - In most cases, NUT is involved in a balanced translocation with the BRD4 gene on chromosome 19p13.1, an event that creates a BRD4-NUT fusion gene.
NUT_BRD4t(15;19) / t(15;19)(q13;p13) / 16435379ewing sarcoma;sarcoma - - A subset of poorly differentiated carcinomas is characterized by the translocation t(15;19)(q13;p13), resulting in a BRD4/NUT fusion gene. /// "The findings show that t(15;19)-BRD4/NUT-positive tumors may arise in locations more typical for other pediatric tumors, such as Ewing sarcoma, and that they not always display epithelial differentiation. " /// We here present the successful treatment of a 10-year-old boy who presented with a BRD4/NUT-positive undifferentiated tumor in the iliac bone.
NUT_BRD4t(15,19) / / 23374840seminoma - - The cell lines also did not contain the BRD4/NUT gene rearrangement [t(15,19)] seen in midline carcinomas nor did they contain overexpressed nuclear protein in testis (NUT) genes.
NUT_BRD4- 22017582squamous cell carcinoma - - NUT midline carcinoma (NMC), an aggressive form of squamous cell carcinoma, is defined by the presence of acquired chromosomal rearrangements involving NUT, usually BRD4-NUT fusion genes and, less commonly, NUT-variant fusion genes involving BRD3 or still-uncharacterized genes.
NUT_BRD4- 24326851- - - Here we describe a classic NMC with a BRD4-NUT fusion gene in a middle-aged woman.
NUT_BRD4t(15;19) / 23128391- PCR - Nuclear protein in testis (NUT)-midline carcinoma (NMC) is a rare, aggressive disease typically presenting with a single t(15;19) translocation that results in the generation of a bromodomain-containing protein 4 (BRD4)-NUT fusion. /// "Thus, the generation of BRD4-NUT fusion transcripts through post-translocation RNA-splicing appears to be a common feature of these carcinomas that has not previously been appreciated, with the mechanism facilitating the expression of alternative isoforms of the fusion. " /// Novel BRD4-NUT fusion isoforms increase the pathogenic complexity in NUT midline carcinoma.. /// These data demonstrate that the novel BRD4-NUT fusion in PER-624 encodes a functional protein that is central to the oncogenic mechanism in these cells.
NUT_BRD4t(15;19) / 24736545- - - The BRD4-NUT fusion oncogene resulting from t(15;19) translocation is required for the abnormal activation of SOX2, which drives the stem cell-like proliferation and cellular transformation in NMC cells. /// These studies identify this stem cell marker as a novel BRD4-NUT target that supports the highly aggressive transforming activity of t(15;19) carcinomas. /// We further demonstrate that BRD4-NUT oncoprotein recruits p300 to stimulate transcription activation and that inhibition of p300 represses SOX2 transcription in NMC cells. /// Our study provides new mechanistic insights for understanding how alteration of BRD4 function by BRD4-NUT oncogene leads to the highly malignant NMC carcinoma. /// "SOX2 knockdown phenocopies the effects of BRD4-NUT inhibition, whereas ectopic SOX2 expression rescues the phenotype. " /// Activation of SOX2 expression by BRD4-NUT oncogenic fusion drives neoplastic transformation in NUT midline carcinoma..
NUT_BRD4- 17934517- - - The BRD3-NUT fusion gene encodes a protein composed of two tandem chromatin-binding bromodomains, an extra-terminal domain, a bipartite nuclear localization sequence, and almost the entirety of NUT that is highly homologous to BRD4-NUT. /// "Consistent with this idea, FRAP studies show that BRD4, BRD4-NUT and BRD3-NUT have significantly slower rates of lateral nuclear diffusion than that of NUT. " /// "In contrast, BRD3-NUT and BRD4-NUT are strictly nuclear, implying that the BRD moiety retains NUT in the nucleus via interactions with chromatin. " /// "To investigate the functional role of BRD-NUT fusion proteins in NMCs, we investigated the effects of siRNA-induced BRD3-NUT and BRD4-NUT withdrawal. "
NUT_BRD4- 26551281proptosis - - Inhibition of the canonical 3' acceptor splice site of NUT intron 1 in cell lines expressing the most common NMC fusion transcripts (PER-403, BRD4-NUT ex11:ex2. /// "Molecular analysis of the tumor tissue identified a novel in-frame BRD4-NUT transcript, with BRD4 exon 15 fused to the last 124 nucleotides of NUT exon 2 (BRD4-NUT ex15:ex2?nt1-585). " /// Detection of low levels of an in-frame BRD4-NUT ex11:ex2?nt1-585 transcript in PER-403 confirmed endogenous splicing from this alternative exon 2 splice site. /// "PER-624, BRD4-NUT ex15:ex2) induced alternative splicing from the same cryptic splice site as identified in the patient. " /// A novel BRD4-NUT fusion in an undifferentiated sinonasal tumor highlights alternative splicing as a contributing oncogenic factor in NUT midline carcinoma..
NUT_BRD419p13.3 / 19p13.13 / 25982285lung cancer - - Gene aberrations include translocation t(15, 19) (q13, p13.1) fusion oncogene BRD4-NUT, DNA repair genes (ERCC1, ERCC2, XRCC1), TGF?1 pathway activation genes (TGFB1, LTBP4), Dyrk1B, and potential oncogenesis protector genes such as NFkB pathway inhibition genes (NFKBIB, PPP1R13L) and EGLN2.
NUT_BRD4t(15;19) / 15994877lung cancer;sarcoma PCR;RT-PCR - However, we also found that the Brd4-NUT fusion augments the inhibition of progression to S phase compared with wild type Brd4. /// "Alteration in cell cycle kinetics is important in tumorigenesis, although the exact role of Brd4-NUT fusion protein in the pathogenesis of lung cancers remains unclear and need to be further elucidated.. "
NUT_BRD4t(15;19) / 12543779- - - Herein we demonstrate that BRD4 is fused with nearly the entire transcript of the novel 15q13 gene, NUT (nuclear protein in testis), forming a 6.4-kb fusion oncogene, BRD4-NUT. /// BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma.. /// "Very few fusion oncogenes have been identified in epithelial tumors, and BRD4-NUT is the first fusion oncogene mechanism identified in a highly lethal form of carcinoma.. "
NUT_BRD4t(11;19)(q12;p13) / t(6;9)(q22-23;p23-24) / t(15;19) / 19p13.1 / 21238915adenoid cystic carcinoma;mucoepidermoid carcinoma - - Because NMC lacks characteristic clinicopathologic features and established therapeutic options, the BRD4-NUT fusion transcript may represent both a diagnostic marker and an optimal target for disease-specific drug therapy.
NUT_BRD4- 20395873- - - The gene BRD4 is its most common translocation partner, forming a BRD4-NUT fusion oncogene. /// BRD4-NUT carcinoma of the mediastinum in a pediatric patient: multidetector computed tomography imaging findings..
NUT_BRD4- 23463074squamous cell carcinoma - - The rearrangements most often take the form of BRD4-NUT fusions, and in a minority of cases, BRD3-NUT or NUT-variant fusions. /// "The oncogenic mechanism of the dual bromodomains and the p300-binding portion of BRD4-NUT is to sequester p300 to localized regions of chromatin, leading to global transcriptional repression and blockade of differentiation. "
NUT_BRD4t(15;19)(q13;p13) / 20676058- - - Knockdown of BRD4-NUT released p300 and restored p53-dependent regulatory mechanisms leading to cell differentiation and apoptosis. /// "Using a patient-derived cell line, we show that p300 sequestration into the BRD4-NUT foci is the principal oncogenic mechanism leading to p53 inactivation. " /// "In this study, we show that, after binding to acetylated chromatin through BRD4 bromodomains, the NUT moiety of the fusion protein strongly interacts with and recruits p300, stimulates its catalytic activity, initiating cycles of BRD4-NUT/p300 recruitment and creating transcriptionally inactive hyperacetylated chromatin domains. "
NUT_BRD4- 26244120- - - It is characterized by its genotypic feature of BRD4-NUT translocation, which is in contrast with other malignant processes that are usually categorized based on their histologic/phenotypic features.
NUT_BRD4t(15;19) / 25512383- - - NUT midline carcinoma (NMC) is a rare but highly aggressive cancer typically caused by the translocation t(15;19), which results in the formation of the BRD4-NUT fusion oncoprotein. /// Mechanistic analysis of the role of bromodomain-containing protein 4 (BRD4) in BRD4-NUT oncoprotein-induced transcriptional activation.. /// "However, the mechanistic details of this BRD4-NUT function remain poorly understood. " /// "We also discovered that, in BRD4-NUT expressed in NMC cells, the NUT moiety of the fusion protein anchored to chromatin by the double bromodomains also stimulates histone hyperacetylation, which causes BRD4 to bind tighter to chromatin. "

ChimerSEQ

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The fusion gene pair NUT--BRD4 information is not available in CHIMERSEQ (CHIMERDB 3.0) database.

ChiTaRS 2.1

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The fusion gene pair NUT--BRD4 information is not available in CHITARS database.

FARE-CAFE

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The fusion gene pair NUT--BRD4 information is not available in FARE-CAFE.

TicDB

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The fusion gene pair NUT--BRD4 information is not available in TicDB.

TUMOR FUSION Gene Data Portal

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The fusion gene pair NUT--BRD4 information is not available in TUMOR FUSION Gene Data Portal.

FusionCancer

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The fusion gene pair NUT--BRD4 information is not available in FusionCancer Database.

ConjoinG

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The fusion gene pair NUT--BRD4 information is not available in ConjoinG Database.

1000Genome

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Fusion gene NUT--BRD4 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 NUT--BRD4 is not 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 NUT--BRD4 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 NUT--BRD4 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 NUT--BRD4 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 NUT--BRD4 information is not available in Babiceanu_Dataset.

Banned_Dataset

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Fusion gene NUT--BRD4 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 NUT--BRD4 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 NUT is a known oncogene according to ONGENE database.


The tail gene BRD4 is a known oncogene according to ONGENE database.

Bushman Cancer Gene Database

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


The tail gene BRD4 is cancer associated according to Bushman Cancer Gene database.

Tumor Gene Set By Uniprot

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The head gene NUT is not a proto-oncogene or tumor suppresor gene according to Uniprot database.
The tail gene BRD4 is not a proto-oncogene or tumor suppresor gene according to Uniprot database.

Oesophagus_Dataset

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Fusion gene NUT--BRD4 is not found in oesophageal tumors from TCGA samples, which are published here.

Gliomas_Dataset

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Fusion gene NUT--BRD4 is not found in the RNA-seq dataset of 272 glioblastomas, published here.

Prostate_Dataset

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The fusion gene pair NUT--BRD4 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 NUT--BRD4 is not found in pancreatic tumor dataset, published here.

GTEx

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Fusion gene NUT--BRD4 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 NUT--BRD4 information is not available in Klijn Dataset.

Fimereli_Dataset

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The fusion gene pair NUT--BRD4 information is not found in Fimereli_Dataset.

Literature

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The fusion gene pair NUT--BRD4 information is not found in known fusion genelist compiled from literature.

Cortex_Dataset

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Fusion gene NUT--BRD4 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 NUT--BRD4 information is not available in ChromothripsisDB database.