French Christopher A, Miyoshi Isao, Kubonishi Ichiro, Grier Holcombe E, Perez-Atayde Antonio R, Fletcher Jonathan A
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Cancer Res. 2003 Jan 15;63(2):304-7.
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.
伴有t(15;19)(q13,p13.1)的低分化癌具有高度侵袭性、临床病程必然致死的特点。19号染色体易位断点靶向BRD4双溴结构域基因，该基因在细胞周期进程调控中发挥作用。在此我们证明，BRD4与新发现的15q13基因NUT（睾丸核蛋白）的几乎整个转录本融合，形成一个6.4kb的融合癌基因BRD4-NUT。NUT与BRD4一样，预计编码一种核蛋白，但与普遍存在的BRD4转录本不同，它仅在睾丸中表达。这些发现建立了一个模型，以阐明异常NUT表达和BRD4功能改变的致癌后果。上皮性肿瘤中鉴定出的融合癌基因非常少，BRD4-NUT是在一种高度致死性癌中鉴定出的首个融合癌基因机制。
