Cancer genetics and epigenetics: two sides of the same coin?

Cancer genetics and epigenetics: two sides of the same coin?
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DOI:
10.1016/j.ccr.2012.06.008
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发表时间:
2012-07-10
期刊:
影响因子:
50.3
通讯作者:
Jones PA
Jones PA
中科院分区:
医学1区
文献类型:
--
作者:
You JS;Jones PA

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表观遗传和遗传改变长期以来被认为是参与致癌的两种独立机制。最近对数千种人类癌症进行全外显子组测序的结果意外地发现了控制表观基因组的基因中的许多失活突变。这些突变有可能破坏 DNA 甲基化模式、组蛋白修饰和核小体定位,从而破坏基因表达。因此,表观基因组的遗传改变会导致癌症,就像表观遗传过程会导致点突变并禁用 DNA 修复功能一样。基因组和表观基因组之间的这种串扰为治疗提供了新的可能性。
Epigenetic and genetic alterations have long been thought of as two separate mechanisms participating in carcinogenesis. A recent outcome of whole exome sequencing of thousands of human cancers has been the unexpected discovery of many inactivating mutations in genes that control the epigenome. These mutations have the potential to disrupt DNA methylation patterns, histone modifications and nucleosome positioning and hence, gene expression. Genetic alteration of the epigenome therefore contributes to cancer just as epigenetic process can cause point mutations and disable DNA repair functions. This crosstalk between the genome and the epigenome offers new possibilities for therapy.
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