Rashid Asif, Issa Jean Pierre J
Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Gastroenterology. 2004 Nov;127(5):1578-88. doi: 10.1053/j.gastro.2004.09.007.
Fifteen years after the first demonstration of epigenetic tumor-suppressor gene inactivation associated with promoter methylation, the field has reached a level of understanding that threatens a re-writing of established biologic concepts. In gastrointestinal malignancies, epigenetic analysis has led to novel hypotheses regarding the etiology of age-associated cancer susceptibility and the interactions between environmental exposures and neoplasia. Methylation profiling has uncovered a distinct pathway to colorectal neoplasia that may arise from a hitherto underestimated precursor lesion, the proximal hyperplastic polyp-serrated adenoma pathway. Epigenetic information has shown promise in clarifying susceptibility to cancer and defining poor prognosis groups in gastrointestinal cancers. Finally, the field has engendered renewed interest in therapeutic targeting of epigenetic regulatory molecules, and several such drugs are currently in clinical trials. It is likely that epigenetic pathways will be integrated in the routine management of gastrointestinal malignancies over the next decade.
在首次证明与启动子甲基化相关的表观遗传肿瘤抑制基因失活15年后，该领域已达到了一个理解水平，这可能会改写既定的生物学概念。在胃肠道恶性肿瘤中，表观遗传分析产生了关于年龄相关癌症易感性的病因以及环境暴露与肿瘤形成之间相互作用的新假说。甲基化谱分析揭示了一条独特的结直肠癌形成途径，该途径可能源于一种迄今被低估的前体病变，即近端增生性息肉-锯齿状腺瘤途径。表观遗传信息在阐明癌症易感性和确定胃肠道癌症的预后不良群体方面显示出了前景。最后，该领域重新激发了对表观遗传调节分子治疗靶点的兴趣，目前有几种此类药物正在进行临床试验。在未来十年，表观遗传途径很可能会被纳入胃肠道恶性肿瘤的常规管理中。
