Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Division of Advanced Surgical Oncology, Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Cancer Sci. 2018 Dec;109(12):3695-3706. doi: 10.1111/cas.13812. Epub 2018 Oct 26.
Promoter DNA methylation, which occurs on cytosine nucleotides across CpG islands, results in gene silencing and represents a major epigenetic alteration in human cancer. Methylation-specific PCR can amplify these modifications as markers in cancer cells. In the present work, we rigorously review the published literatures describing DNA methylation in the promoters of critical tumor suppressor genes; detection of promoter DNA methylation in various body fluids permits early detection of cancer cells during perioperative courses of clinical treatment. The latest whole-genome comprehensive explorations identified excellent epigenetic biomarkers that could be detected at high frequency with high specificity; these biomarkers, which are designated highly relevant methylation genes (HRMG), permit the discrimination of tumor tissues from the corresponding normal tissues; these markers are also associated with unique cancer phenotypes, including dismal prognosis. In humans, HRMG include the CDO1, GSHR, RASSF1 and SFRP1 genes, with these markers permitting discrimination depending on the organs tested. The combination of several HRMG increased the early detection of cancer and exhibited reliable surveillance potential in human body fluids. Cancer clinics using such epigenetic biomarkers are entering a new era of enhanced decision-making with the potential for improved cancer prognosis.
启动子 DNA 甲基化发生在 CpG 岛上的胞嘧啶核苷酸上,导致基因沉默,是人类癌症中主要的表观遗传改变。甲基化特异性 PCR 可以扩增这些修饰作为癌细胞中的标记物。在本工作中,我们严格审查了描述关键肿瘤抑制基因启动子中 DNA 甲基化的已发表文献;在各种体液中检测启动子 DNA 甲基化可在临床治疗的围手术期早期检测癌细胞。最新的全基因组综合探索确定了优秀的表观遗传生物标志物,可以高特异性和高频率检测到;这些生物标志物被指定为高度相关的甲基化基因(HRMG),可区分肿瘤组织和相应的正常组织;这些标志物还与独特的癌症表型相关,包括预后不良。在人类中,HRMG 包括 CDO1、GSHR、RASSF1 和 SFRP1 基因,这些标志物可根据测试的器官进行区分。几种 HRMG 的组合增加了癌症的早期检测,并在人体体液中表现出可靠的监测潜力。使用这种表观遗传生物标志物的癌症临床正在进入一个新的决策增强时代,具有改善癌症预后的潜力。