BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma.
The poorly differentiated carcinoma with t(15;19)(q13, p13.1) is characterized by its highly aggressive, invariably lethal clinical course. The chromosome 19 translocation breakpoint targets the BRD4 double bromodomain-containing gene, which functions in regulation of cell cycle progression. 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. NUT, like BRD4, is predicted to encode a nuclear protein but, unlike the ubiquitous BRD4 transcript, is expressed only in testis. These findings establish a model to elucidate the oncogenic consequences of unscheduled NUT expression and altered BRD4 function. 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.
French
Christopher A
CA
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. cfrench@partners.org
Miyoshi
Isao
I
Kubonishi
Ichiro
I
Grier
Holcombe E
HE
Perez-Atayde
Antonio R
AR
Fletcher
Jonathan A
JA
D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D020224:Expressed Sequence Tags; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics; D013737:Testis / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D000092468:Bromodomain Containing Proteins
D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins; C471990:BRD4-NUT fusion oncogene protein, human; C000630260:NUTM1 protein, human