Department of Pathology and Hutchison/MRC Research Centre, University of Cambridge, Cambridge CB2 0XZ, UK.
J Pathol. 2010 Jan;220(2):244-54. doi: 10.1002/path.2632.
It has been known for 25 years that fusion genes play a central role in leukaemias and sarcomas but they have been neglected in the common carcinomas, largely because of technical limitations of cytogenetics. In the last few years it has emerged that gene fusions, caused by chromosome translocations, inversions, deletions, etc., are important in the common epithelial cancers, such as prostate and lung carcinoma. Most prostate cancers, for example, have an androgen-regulated fusion of one of the ETS transcription factor gene family. Early results of genome-wide searches for gene fusions in breast and other epithelial cancers suggest that most individual tumours will have several fused genes. Fusion genes are exceptionally powerful mutations. In their simplest form they can turn on expression by promoter insertion but they can also, for example, force dimerization of a protein or change its subcellular location. They are correspondingly important clinically, in classification and management and as targets for therapy. This review surveys what we know of fusion genes in the carcinomas, summarizes the technical advances that now make it possible to search systematically for such genes, and concludes by putting fusion genes into the current picture of mutation in cancers.
25 年来，人们已经知道融合基因在白血病和肉瘤中起着核心作用，但在常见的癌中却被忽视了，这在很大程度上是因为细胞遗传学的技术限制。在过去的几年中，人们已经发现，由染色体易位、倒位、缺失等引起的基因融合，在常见的上皮性癌如前列腺癌和肺癌中是很重要的。例如，大多数前列腺癌都有一种雄激素调节的 ETS 转录因子基因家族的融合。对乳腺癌和其他上皮性癌中基因融合的全基因组搜索的早期结果表明，大多数肿瘤都有几个融合基因。融合基因是非常强大的突变。在最简单的形式中，它们可以通过启动子插入来激活表达，但它们也可以迫使蛋白质二聚化或改变其亚细胞位置。它们在临床上也非常重要，在分类和管理以及作为治疗靶点方面都很重要。这篇综述调查了我们在癌中对融合基因的了解，总结了现在可以系统地搜索这些基因的技术进展，并在最后将融合基因纳入癌症突变的当前图景中。
