Kluzek Katarzyna, Bluyssen Hans A, Wesoly Joanna
Department of Human Molecular Genetics, Laboratory of High Throughput Technologies, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University in Poznan, Umultowska 89, 61-614 Poznan, Poland.
J Kidney Cancer VHL. 2015 May 28;2(3):90-104. doi: 10.15586/jkcvhl.2015.33. eCollection 2015.
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of all kidney tumors. During the last few years, epigenetics has emerged as an important mechanism in ccRCC pathogenesis. Recent reports, involving large-scale methylation and sequencing analyses, have identified genes frequently inactivated by promoter methylation and recurrent mutations in genes encoding chromatin regulatory proteins. Interestingly, three of detected genes (PBRM1, SETD2 and BAP1) are located on chromosome 3p, near the VHL gene, inactivated in over 80% ccRCC cases. This suggests that 3p alterations are an essential part of ccRCC pathogenesis. Moreover, most of the proteins encoded by these genes cooperate in histone H3 modifications. The aim of this review is to summarize the latest discoveries shedding light on deregulation of chromatin machinery in ccRCC. Newly described ccRCC-specific epigenetic alterations could potentially serve as novel diagnostic and prognostic biomarkers and become an object of novel therapeutic strategies.
透明细胞肾细胞癌（ccRCC）是所有肾肿瘤中最常见的亚型。在过去几年中，表观遗传学已成为ccRCC发病机制中的一个重要机制。最近涉及大规模甲基化和测序分析的报告已经鉴定出经常因启动子甲基化而失活的基因以及编码染色质调节蛋白的基因中的复发性突变。有趣的是，检测到的三个基因（PBRM1、SETD2和BAP1）位于3号染色体上，靠近VHL基因，在超过80%的ccRCC病例中失活。这表明3p改变是ccRCC发病机制的重要组成部分。此外，这些基因编码的大多数蛋白质在组蛋白H3修饰中协同作用。本综述的目的是总结最新发现，以阐明ccRCC中染色质机制的失调。新描述的ccRCC特异性表观遗传改变可能作为新的诊断和预后生物标志物，并成为新治疗策略的对象。
