Miyamoto Kazuaki, Ushijima Toshikazu
Carcinogenesis Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 Japan.
Jpn J Clin Oncol. 2005 Jun;35(6):293-301. doi: 10.1093/jjco/hyi088. Epub 2005 Jun 1.
Epigenetic abnormalities, such as aberrant methylation of CpG islands, are inherited over cell divisions, and play important roles in carcinogenesis. Aberrant methylation of CpG islands specific to tumor cells can be used as a marker to detect cancer cells or cancer-derived DNA, taking advantage of the high sensitivity of methods to detect aberrant methylation. Methylations of specific genes or methylation patterns of groups of genes were found to be associated with responses to chemotherapeutics and prognosis. Methylation in non-cancerous tissues is now attracting attention as a tumor risk marker, and is emerging as a target for cancer prevention. Epigenetic alterations are potentially reversible. The use of DNA demethylating agents has turned out to be effective for hematological malignancies, and is being tested in solid tumors. Histone deacetylase inhibitors and methods for gene-specific epigenetic modification are being developed. Application of epigenetics to cancer diagnostics and therapeutics, and possibly to cancer prevention, is coming into clinics.
表观遗传异常,如CpG岛的异常甲基化,可在细胞分裂过程中遗传,并在致癌过程中发挥重要作用。利用检测异常甲基化方法的高灵敏度,肿瘤细胞特有的CpG岛异常甲基化可作为检测癌细胞或癌症衍生DNA的标志物。发现特定基因的甲基化或基因组的甲基化模式与化疗反应和预后相关。非癌组织中的甲基化作为一种肿瘤风险标志物正受到关注,并正在成为癌症预防的靶点。表观遗传改变可能是可逆的。DNA去甲基化剂已被证明对血液系统恶性肿瘤有效,目前正在实体瘤中进行测试。组蛋白脱乙酰酶抑制剂和基因特异性表观遗传修饰方法正在开发中。表观遗传学在癌症诊断和治疗以及可能的癌症预防中的应用正在进入临床。