Aberrant CpG-island methylation has non-random and tumour-type-specific patterns
Aberrant CpG-island methylation has non-random and tumour-type-specific patterns
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DOI：
10.1038/72785
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发表时间：
2000-02-01
期刊：
影响因子：
30.8
通讯作者：
Plass, C
中科院分区：
文献类型：
--
作者：
Costello, JF;Fr端hwald, MC;Plass, C
CpG 岛经常包含基因启动子或外显子 (1)，并且在正常细胞中通常未甲基化 (1-3)。 CPG 岛的甲基化与复制延迟、染色质浓缩和转录起始抑制相关 (4-7)。对人类癌症中异常 CpG 岛甲基化的研究主要采用候选基因方法，并重点关注基因组中估计 45,000 个 CpG 岛(8) 中的不到 15 个。在这里，我们使用限制性标志基因组扫描 (9) (RLGS) 对 98 个主要人类谣言中的每一个中的 1,184 个未选择的 CpG 岛的甲基化状态进行了全球分析。我们估计，在谣言中，基因组中的 45,000 个 CpG 岛（范围为 0 至 4,500）中平均有 600 个 CpG 岛（包括早期肿瘤）发生异常甲基化。我们确定了每种肿瘤类型共有的 CpG 岛甲基化模式，以及显示不同肿瘤类型特异性的模式和靶点。通过在培养的肿瘤细胞中进行实验去甲基化，许多这些基因的表达被重新激活。因此，CpG 岛特定亚群的甲基化可能对特定肿瘤类型产生影响。
CpG islands frequently contain gene promoters or exons(1) and are usually unmethylated in normal cells(1-3). Methylation of CPG islands is associated with delayed replication, condensed chromatin and inhibition of transcription initiation(4-7). The investigation of aberrant CpG-island methylation in human cancer has primarily taken a candidate gene approach, and has focused on less than 15 of the estimated 45,000 CpG islands(8) in the genome. Here we report a global analysis of the methylation status of 1,184 unselected CpG islands in each of 98 primary human rumours using restriction landmark genomic scanning(9) (RLGS). We estimate that an average of 600 CpG islands (range of 0 to 4,500) of the 45,000 in the genome were aberrantly methylated in the rumours, including early stage tumours. We identified patterns of CpG;island methylation that were shared within each tumour type, together with patterns and targets that displayed distinct tumour-type specificity. The expression of many of these genes was reactivated by experimental demethylation in cultured tumour cells. Thus, the methylation of particular subsets of CpG islands may have consequences for specific tumour types.