Ushijima Toshikazu, Yoshida Satoshi
Division of Epigenomics, National Cancer Center Research Institute.
Nihon Rinsho. 2012 Oct;70(10):1705-14.
Genetic and epigenetic alterations are induced during gastric carcinogenesis. Infection by H. pylori markedly increases induction of both alterations, and inflammation triggered by the infection is critical for induction of aberrant DNA methylation (epigenetic alterations). Oncogenes, such as PIK3CA, CTNNB1, KRAS, and ERBB2, are activated by point mutations and gene amplification. Tumor-suppressor genes, such as TP53, CDH1, CDKN2A, and MLH1, are inactivated by mutations, and more frequently by aberrant methylation if they have promoter CpG islands. The information on the activated signaling pathway, such as the ERBB2-MAPK signaling pathway, is now becoming useful for patient stratification. Comprehensive analysis of genetic and epigenetic alterations in gastric cancers is expected to lead to more occasions of translation.
在胃癌发生过程中会诱导产生基因和表观遗传改变。幽门螺杆菌感染显著增加了这两种改变的诱导，并且该感染引发的炎症对于异常DNA甲基化（表观遗传改变）的诱导至关重要。诸如PIK3CA、CTNNB1、KRAS和ERBB2等癌基因通过点突变和基因扩增被激活。诸如TP53、CDH1、CDKN2A和MLH1等肿瘤抑制基因通过突变失活，如果它们具有启动子CpG岛，则更频繁地通过异常甲基化失活。关于激活的信号通路，如ERBB2-MAPK信号通路的信息，现在对于患者分层变得有用。对胃癌中基因和表观遗传改变的综合分析有望带来更多的转化机会。
