Evidence for an instructive mechanism of de novo methylation in cancer cells
Evidence for an instructive mechanism of de novo methylation in cancer cells
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DOI：
10.1038/ng1719
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发表时间：
2006-02-01
期刊：
影响因子：
30.8
通讯作者：
Simon, I
中科院分区：
文献类型：
--
作者：
Keshet, I;Schlesinger, Y;Simon, I
DNA甲基化在正常哺乳动物发育期间的基因表达调控中起作用，但也可以介导癌症和其他疾病中CpG岛基因的表观遗传沉默。许多个体基因（包括肿瘤抑制基因）已被证明在特定肿瘤类型中经历从头甲基化，但这一过程中固有的生物学逻辑尚不清楚。为了解释这一机制，我们采用了一种新的方法来检测CpG岛DNA甲基化，可以与微阵列技术一起使用。全基因组分析表明，肿瘤特异性甲基化基因属于不同的功能类别，在其启动子中具有共同的序列基序，并在染色体上的簇中发现。此外，许多已经在正常细胞中被抑制。这些结果与癌症相关的从头甲基化可能通过指导性机制产生的假设一致。
DNA methylation has a role in the regulation of gene expression during normal mammalian development but can also mediate epigenetic silencing of CpG island genes in cancer and other diseases. Many individual genes ( including tumor suppressors) have been shown to undergo de novo methylation in specific tumor types, but the biological logic inherent in this process is not understood. To decipher this mechanism, we have adopted a new approach for detecting CpG island DNA methylation that can be used together with microarray technology. Genome-wide analysis by this technique demonstrated that tumor-specific methylated genes belong to distinct functional categories, have common sequence motifs in their promoters and are found in clusters on chromosomes. In addition, many are already repressed in normal cells. These results are consistent with the hypothesis that cancer-related de novo methylation may come about through an instructive mechanism.