Zhu Lila, Li Xinyu, Yuan Ying, Dong Caixia, Yang Mengyuan
Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Front Oncol. 2021 Apr 23;11:653222. doi: 10.3389/fonc.2021.653222. eCollection 2021.
The adenomatous polyposis coli () gene, known as tumor suppressor gene, has the two promoters 1A and 1B. Researches on have usually focused on its loss-of-function variants causing familial adenomatous polyposis. Hypermethylation, however, which is one of the key epigenetic alterations of the CpG sequence, is also associated with carcinogenesis in various cancers. Accumulating studies have successively explored the role of hypermethylation in gastrointestinal (GI) tumors, such as in esophageal, colorectal, gastric, pancreatic, and hepatic cancer. In sporadic colorectal cancer, the hypermethylation of CpG island in is even considered as one of the primary causative factors. In this review, we systematically summarized the distribution of gene methylation in various GI tumors, and attempted to provide an improved general understanding of DNA methylation in GI tumors. In addition, we included a robust overview of demethylating agents available for both basic and clinical researches. Finally, we elaborated our findings and perspectives on the overall situation of gene methylation in GI tumors, aiming to explore the potential research directions and clinical values.
腺瘤性结肠息肉病(APC)基因作为一种肿瘤抑制基因,有1A和1B两个启动子。对APC的研究通常集中在其导致家族性腺瘤性息肉病的功能丧失变体上。然而,高甲基化作为APC基因启动子区域CpG岛的关键表观遗传改变之一,也与多种癌症的致癌作用相关。越来越多的研究相继探讨了APC基因高甲基化在胃肠道(GI)肿瘤中的作用,如食管癌、结直肠癌、胃癌、胰腺癌和肝癌。在散发性结直肠癌中,APC基因启动子区域CpG岛的高甲基化甚至被认为是主要致病因素之一。在本综述中,我们系统地总结了APC基因甲基化在各种胃肠道肿瘤中的分布,并试图增进对胃肠道肿瘤中DNA甲基化的总体认识。此外,我们还全面概述了可用于基础研究和临床研究的去甲基化剂。最后,我们阐述了关于胃肠道肿瘤中APC基因甲基化总体情况的研究结果和观点,旨在探索潜在的研究方向和临床价值。