Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an 710061, People's Republic of China.
Clin Chim Acta. 2013 Sep 23;424:53-65. doi: 10.1016/j.cca.2013.05.002. Epub 2013 May 10.
Gastric cancer is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide. Over 70% of new cases and deaths occur in developing countries. In the early years of the molecular biology revolution, cancer research mainly focuses on genetic alterations, including gastric cancer. Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Recent advancements in the rapidly evolving field of cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer, including DNA methylation, histone modifications, nucleosome positioning, noncoding RNAs, and microRNAs. Aberrant DNA methylation in the promoter regions of gene, which leads to inactivation of tumor suppressor and other cancer-related genes in cancer cells, is the most well-defined epigenetic hallmark in gastric cancer. The advantages of gene methylation as a target for detection and diagnosis of cancer in biopsy specimens and non-invasive body fluids such as serum and gastric washes have led to many studies of application in gastric cancer. This review focuses on the most common and important phenomenon of epigenetics, DNA methylation, in gastric cancer and illustrates the impact epigenetics has had on this field.
胃癌是最常见的恶性肿瘤之一,仍是全球癌症相关死亡的第二大主要原因。超过 70%的新发病例和死亡发生在发展中国家。在分子生物学革命的早期,癌症研究主要集中在遗传改变上,包括胃癌。表观遗传机制对于哺乳动物正常发育和维持组织特异性基因表达模式至关重要。表观遗传过程的破坏可导致基因功能改变和恶性细胞转化。最近,在癌症表观遗传学这一快速发展的领域取得了进展,表明癌症中表观遗传机制的每个组成部分都发生了广泛的重编程,包括 DNA 甲基化、组蛋白修饰、核小体定位、非编码 RNA 和 microRNAs。在胃癌中,基因启动子区域的异常 DNA 甲基化导致肿瘤抑制基因和其他与癌症相关基因的失活,这是最明确的表观遗传标志。基因甲基化作为检测和诊断活检标本和非侵入性体液(如血清和胃液)中癌症的靶点具有优势,这促使人们对其在胃癌中的应用进行了大量研究。本文重点介绍了胃癌中最常见和最重要的表观遗传现象——DNA 甲基化,并说明了表观遗传学对该领域的影响。