BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma.
BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma.
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发表时间：
2003-01
期刊：
影响因子：
11.2
通讯作者：
C. French;I. Miyoshi;I. Kubonishi;H. Grier;A. Perez-Atayde;J. Fletcher
中科院分区：
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作者：
C. French;I. Miyoshi;I. Kubonishi;H. Grier;A. Perez-Atayde;J. Fletcher
具有t(15；19)(q13，p13.1)的低分化癌具有高度侵袭性，总是致命的临床病程。19号染色体易位断裂点针对的是BRD4双溴结构域基因，该基因在调节细胞周期进程中发挥作用。在这里，我们证明了BRD4与新的15q13基因NUT(睾丸核蛋白)的几乎整个转录本融合，形成了一个6.4kb的融合癌基因BRD4-NUT。坚果和BRD4一样，被预测编码一种核蛋白，但与普遍存在的BRD4转录本不同，它只在睾丸中表达。这些发现建立了一个模型来阐明非程序性NUT表达和BRD4功能改变的致癌后果。在上皮性肿瘤中发现的融合癌基因很少，而BRD4-NUT是第一个在高度致命性癌症中发现的融合癌基因机制。
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.