DNA hypomethylation in cancer cells.
DNA hypomethylation in cancer cells.
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DOI：
10.2217/epi.09.33
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发表时间：
2009-12
期刊：
影响因子：
3.8
通讯作者：
Ehrlich M
中科院分区：
文献类型：
--
作者：
Ehrlich M
DNA低甲基化是人类肿瘤中发现的最初表观遗传异常。然而，在1983年由两个实验室独立发现后的几十年里，它经常被忽视为一种不受欢迎的并发症，几乎所有的注意力都集中在癌症中沉默的基因启动子的超甲基化上（例如，肿瘤抑制基因）。由于随后的研究表明，癌症中DNA的整体低甲基化与重复DNA元件的关系最为密切，因此癌症相关DNA低甲基化仍然很少受到关注。癌症中的DNA低甲基化不再被认为是一种奇怪的现象，因为最近的高分辨率全基因组研究证实，DNA低甲基化几乎是癌症中基因组高甲基化的恒定伴随物，只是通常（但不总是）在不同的序列中。癌症中单个CpG二联体的甲基化变化不仅对区域背景具有高度依赖性，而且对邻近位点也具有高度依赖性。在癌发生过程中，DNA去甲基化可能涉及半甲基化的二联体作为中间体，随后在两条链上扩散甲基化的丢失。在这篇综述中，积极的DNA去甲基化和癌症相关的DNA低甲基化与癌症干细胞的关系进行了讨论。DNA低甲基化在癌症中的生物学意义和临床相关性的证据正在积累，并且癌症相关的去甲基化和从头甲基化是高度动态的过程。
DNA hypomethylation was the initial epigenetic abnormality recognized in human tumors. However, for several decades after its independent discovery by two laboratories in 1983, it was often ignored as an unwelcome complication, with almost all of the attention on the hypermethylation of promoters of genes that are silenced in cancers (e.g., tumor-suppressor genes). Because it was subsequently shown that global hypomethylation of DNA in cancer was most closely associated with repeated DNA elements, cancer linked-DNA hypomethylation continued to receive rather little attention. DNA hypomethylation in cancer can no longer be considered an oddity, because recent high-resolution genome-wide studies confirm that DNA hypomethylation is the almost constant companion to hypermethylation of the genome in cancer, just usually (but not always) in different sequences. Methylation changes at individual CpG dyads in cancer can have a high degree of dependence not only on the regional context, but also on neighboring sites. DNA demethylation during carcinogenesis may involve hemimethylated dyads as intermediates, followed by spreading of the loss of methylation on both strands. In this review, active demethylation of DNA and the relationship of cancer-associated DNA hypomethylation to cancer stem cells are discussed. Evidence is accumulating for the biological significance and clinical relevance of DNA hypomethylation in cancer, and for cancer-linked demethylation and de novo methylation being highly dynamic processes.
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