There is overwhelming evidence that DNA methylation patterns are altered in cancer. Methylation of CG-rich islands in regulatory regions of genes marks them for transcriptional silencing. Multiple genes, which confer selective advantage upon cancer cells such as tumor suppressors, adhesion molecules, inhibitors of angiogenesis and repair enzymes are silenced. In parallel, tumor cell genomes are globally less methylated than their normal counterparts. In contrast to regional hypermethylation, this loss of methylation in cancer cells occurs in sparsely distributed CG sequences. We now understand that DNA methylation machineries might include a number of DNA methyltransferases, proteins that direct DNA methyltransferases to specific promoters, chromatin modifying enzymes as well as demethylases. There is also data to suggest that pharmacological down regulation of some members of the DNA methylation machinery could inhibit cancer in vitro, in vivo and in clinical trials. Understanding which functions of DNA methylation machinery are critical for cancer is essential for the design of inhibitors of the DNA methylation machinery as anticancer agents. This review discusses the possible role of DNA methyltranferases and demethylases in tumorigenesis and the possible pharmacological and therapeutic implications of the DNA methylation machinery.

中文翻译：

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在癌症中靶向DNA甲基化。

有大量证据表明，DNA甲基化模式在癌症中发生了改变。基因调控区域中富含CG的岛的甲基化标记了它们的转录沉默。使赋予癌细胞选择性优势的多个基因如肿瘤抑制因子，粘附分子，血管生成抑制剂和修复酶沉默。与此平行，肿瘤细胞基因组的甲基化程度总体上低于正常情况。与区域性高甲基化相反，癌细胞中这种甲基化的丧失发生在稀疏分布的CG序列中。我们现在了解到，DNA甲基化机制可能包括许多DNA甲基转移酶，将DNA甲基转移酶引导至特定启动子的蛋白，染色质修饰酶以及脱甲基酶。也有数据表明，DNA甲基化机制的某些成员的药理学下调可以在体外，体内和临床试验中抑制癌症。了解DNA甲基化机制的哪些功能对癌症至关重要，这对于设计DNA甲基化机制的抑制剂作为抗癌剂至关重要。这篇综述讨论了DNA甲基转移酶和脱甲基酶在肿瘤发生中的可能作用以及DNA甲基化机制的可能的药理和治疗意义。