Cooper C S, Foster C S
Male Urological Cancer Research Centre, Institute of Cancer Research, Sutton, Surrey, UK.
Br J Cancer. 2009 Jan 27;100(2):240-5. doi: 10.1038/sj.bjc.6604771. Epub 2008 Nov 11.
Substantial evidence now supports the view that epigenetic changes have a role in the development of human prostate cancer. Analyses of the patterns of epigenetic alteration are providing important insights into the origin of this disease and have identified specific alterations that may serve as useful diagnostic and prognostic biomarkers. Examination of cancer methylation patterns supports a stem cell origin of prostate cancer. It is well established that methylation of GSTpi is a marker of prostate cancer, and global patterns of histone marking appear to be linked to cancer prognosis with levels of acetylated histones H3K9, H3K18, and H4K12, and of dimethylated H4R3 and H3K4, dividing low-grade prostate cancer (Gleason 6 or less) into two prognostically separate groups. Elevated levels of several components of the polycomb group protein complex, EZH2, BMI1, and RING1, can also act as biomarkers of poor clinical outcome. Many components of the epigenetic machinery, including histone deacetylase (whose expression level is linked to the TMPRSS2:ERG translocation) and the histone methylase EZH2, are potential therapeutic targets. The recent discovery of the role of small RNAs in governing the epigenetic status of individual genes offers exciting new possibilities in therapeutics and chemoprevention.
现在有大量证据支持表观遗传变化在人类前列腺癌发展中起作用这一观点。对表观遗传改变模式的分析为该疾病的起源提供了重要见解，并确定了可能作为有用诊断和预后生物标志物的特定改变。对癌症甲基化模式的研究支持前列腺癌起源于干细胞。众所周知，GSTpi甲基化是前列腺癌的一个标志物，组蛋白标记的整体模式似乎与癌症预后相关，乙酰化组蛋白H3K9、H3K18和H4K12以及二甲基化H4R3和H3K4的水平将低级别前列腺癌（Gleason评分6分及以下）分为两个预后不同的组。多梳蛋白复合体的几个成分EZH2、BMI1和RING1水平升高也可作为临床预后不良的生物标志物。表观遗传机制的许多成分，包括组蛋白去乙酰化酶（其表达水平与TMPRSS2:ERG易位有关）和组蛋白甲基转移酶EZH2，都是潜在的治疗靶点。小RNA在调控单个基因表观遗传状态方面作用的最新发现为治疗和化学预防提供了令人兴奋的新可能性。
