Cancer and Stem Cell Biology Programme, Duke-NUS Medical School, 8 College Road, 169857 Singapore.
Division of Epigenomics, National Cancer Centre Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Nat Rev Gastroenterol Hepatol. 2017 Aug;14(8):467-478. doi: 10.1038/nrgastro.2017.53. Epub 2017 May 17.
Gastric cancer is a deadly malignancy afflicting close to a million people worldwide. Patient survival is poor and largely due to late diagnosis and suboptimal therapies. Disease heterogeneity is a substantial obstacle, underscoring the need for precision treatment strategies. Studies have identified different subgroups of gastric cancer displaying not just genetic, but also distinct epigenetic hallmarks. Accumulating evidence suggests that epigenetic abnormalities in gastric cancer are not mere bystander events, but rather promote carcinogenesis through active mechanisms. Epigenetic aberrations, induced by pathogens such as Helicobacter pylori, are an early component of gastric carcinogenesis, probably preceding genetic abnormalities. This Review summarizes our current understanding of the gastric cancer epigenome, highlighting key advances in recent years in both tumours and pre-malignant lesions, made possible through targeted and genome-wide technologies. We focus on studies related to DNA methylation and histone modifications, linking these findings to potential therapeutic opportunities. Lessons learned from the gastric cancer epigenome might also prove relevant for other gastrointestinal cancers.
胃癌是一种致命的恶性肿瘤，影响着全球近百万人。患者的生存率很低，这主要是由于诊断较晚和治疗效果不佳。疾病异质性是一个巨大的障碍，强调了需要精准治疗策略。研究已经确定了胃癌的不同亚群，这些亚群不仅在遗传上，而且在表观遗传特征上也存在明显的差异。越来越多的证据表明，胃癌中的表观遗传异常不是偶然事件，而是通过积极的机制促进了癌变。幽门螺杆菌等病原体引起的表观遗传异常是胃癌发生的早期组成部分，可能早于遗传异常。这篇综述总结了我们目前对胃癌表观基因组的理解，强调了近年来在肿瘤和癌前病变方面的重要进展，这得益于靶向和全基因组技术。我们重点关注与 DNA 甲基化和组蛋白修饰相关的研究，将这些发现与潜在的治疗机会联系起来。从胃癌表观基因组中获得的经验教训可能也与其他胃肠道癌症有关。
