Wu William Kk, Yu Jun, Chan Matthew Tv, To Ka F, Cheng Alfred Sl
Department of Anaesthesia and Intensive Care, Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.
State Key Laboratory of Digestive Diseases, Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.
J Pathol. 2016 Jul;239(3):245-9. doi: 10.1002/path.4731. Epub 2016 May 20.
Epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodelling and microRNAs, convert environmental signals to transcriptional outputs but are commonly hijacked by pathogenic microorganisms. Recent advances in cancer epigenomics have shed new light on the importance of epigenetic deregulation in Helicobacter pylori- and Epstein-Barr virus (EBV)-driven gastric tumourigenesis. Moreover, it is becoming apparent that epigenetic mechanisms interact through crosstalk and feedback loops, which modify global gene expression patterns. The SWI/SNF remodelling complexes are commonly involved in gastric cancers associated with H. pylori or EBV through different mechanisms, including microRNA-mediated deregulation and genetic mutations. While H. pylori causes epigenetic silencing of tumour-suppressor genes to deregulate cellular pathways, EBV-positive tumours exhibit a widespread and distinctive DNA hypermethylation profile. Given the early successes of epigenetic drugs in haematological malignancies, further studies are mandated to enrich and translate our understanding of combinatorial epigenetic deregulation in gastric cancers into interventional strategies in the clinic. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
表观遗传机制，包括DNA甲基化、组蛋白修饰、染色质重塑和微小RNA，可将环境信号转化为转录输出，但常被致病微生物利用。癌症表观基因组学的最新进展为表观遗传失调在幽门螺杆菌和爱泼斯坦-巴尔病毒（EBV）驱动的胃癌发生中的重要性提供了新的线索。此外，表观遗传机制通过相互作用和反馈回路相互作用，从而改变整体基因表达模式这一点也变得越来越明显。SWI/SNF重塑复合体通常通过不同机制参与与幽门螺杆菌或EBV相关的胃癌，这些机制包括微小RNA介导的失调和基因突变。幽门螺杆菌会导致肿瘤抑制基因的表观遗传沉默，从而使细胞通路失调，而EBV阳性肿瘤则表现出广泛且独特的DNA高甲基化谱。鉴于表观遗传药物在血液系统恶性肿瘤中取得的初步成功，有必要进一步开展研究，以丰富我们对胃癌中组合表观遗传失调的理解，并将其转化为临床干预策略。版权所有© 2016英国及爱尔兰病理学会。由约翰·威利父子有限公司出版。
