Kumar-Sinha Chandan, Tomlins Scott A, Chinnaiyan Arul M
Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai 410208, India.
Trends Mol Med. 2006 Nov;12(11):529-36. doi: 10.1016/j.molmed.2006.09.005. Epub 2006 Sep 29.
Chromosomal aberrations that accompany carcinogenesis have been documented for almost half a century, with gene fusions being the most prevalent type of aberration. Gene fusions leading to generation of aberrant fusion proteins or aberrant expression of normal proteins are a potent route to carcinogenesis and have recently emerged as attractive therapeutic targets. Intriguingly, although gene fusions have been widely observed in hematological malignancies, they have been far less frequently described in the more-common epithelial carcinomas. It has been recently proposed that technical issues, rather than any fundamental dichotomy between hematological and solid cancers, account for the under-representation of gene fusions in epithelial cancers. Recent reports from our group support this contention and provide evidence of widespread recurrent gene fusions in prostate cancer using a novel analysis of gene-expression profiles. Here, we provide an appraisal of the state of the knowledge of gene fusions in epithelial cancers. Future implications of gene fusions in common epithelial cancers are also discussed.
伴随致癌作用的染色体畸变已有近半个世纪的记录,基因融合是最常见的畸变类型。导致异常融合蛋白产生或正常蛋白异常表达的基因融合是致癌的一条有效途径,并且最近已成为有吸引力的治疗靶点。有趣的是,尽管基因融合在血液系统恶性肿瘤中已被广泛观察到,但在更常见的上皮癌中却很少被描述。最近有人提出,技术问题而非血液系统癌症与实体癌之间的任何根本差异,是上皮癌中基因融合报道不足的原因。我们小组最近的报告支持这一观点,并通过对基因表达谱的新分析提供了前列腺癌中广泛存在复发性基因融合的证据。在此,我们对上皮癌中基因融合的知识现状进行评估。还讨论了基因融合在常见上皮癌中的未来意义。