卵巢癌表遗传学研究进展

Advances of epigenetics in ovarian cancer

表遗传学的分子机制包括DNA甲基化、组蛋白修饰、染色质改型和RNA干涉等,它们在基因转录调控过程中起重要作用。DNA甲基化和组蛋白乙酰化是表遗传学调控基因表达的两种主要方式,DNA低甲基化和组蛋白乙酰化可促进基因表达,DNA高甲基化和组蛋白去乙酰化可抑制基因表达,DNA甲基化和组蛋白乙酰化相互影响。DNA甲基化在卵巢癌的发生、发展中起重要作用,若干肿瘤抑制基因启动子区异常甲基化与卵巢癌的形成密切相关,包括RASSF1A、BRCA1、p16、hMLH1和CDH1等。多个抑癌基因异常甲基化作为一种分子生物学指标可能用于卵巢癌临床诊断、肿瘤分型及预后判断,而且DNA甲基化异常可能用于卵巢癌化疗疗效判断。DNA去甲基化制剂及组蛋白脱乙酰基酶抑制剂可能用于卵巢癌的临床治疗。

Epigenetics is defined as modifications of the genome, heritable during cell division, that do not involve a change in the DNA sequence. Epigenetics includes DNA methylation, histone modification, chromatin remodeling and RNA interference molecularly, which play important roles in gene expressing regulation. DNA methylation and histone acetylation are the two most widely studied epigenetic changes which regulate gene expression. DNA hypomethylation and hyperacetylation can up-regulate gene expression, and DNA hypermethylation and hypoacetylation can down-regulate gene expression. DNA methylation and histone acetylation interplay closely. Abnormal DNA methylation plays important roles in the course of carcinogenesis and development in ovarian cancer. Promoter hypermethylation of several TSGs play crucial roles in carcinogenesis of ovarian cancer, including RASSF1A, BRCA1, p16, hMLH1, CDH1 and so on. As a molecular biomarker, hypermethylation of several TSGs can be used in diagnosis,tumor typing as well as prognosis predicting, and which can also be used in predicting effects of chemotherapy. DNA demethlylated agents and histone deacetylase inhibitors may be used in treatment of ovarian carcinoma.