Costello J F, Frühwald M C, Smiraglia D J, Rush L J, Robertson G P, Gao X, Wright F A, Feramisco J D, Peltomäki P, Lang J C, Schuller D E, Yu L, Bloomfield C D, Caligiuri M A, Yates A, Nishikawa R, Su Huang H, Petrelli N J, Zhang X, O'Dorisio M S, Held W A, Cavenee W K, Plass C
[1] Ludwig Institute for Cancer Research, University of California-San Diego, La Jolla, California, USA.
Nat Genet. 2000 Feb;24(2):132-8. doi: 10.1038/72785.
CpG islands frequently contain gene promoters or exons and are usually unmethylated in normal cells. Methylation of CpG islands is associated with delayed replication, condensed chromatin and inhibition of transcription initiation. 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 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 tumours using restriction landmark genomic scanning (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 tumours, 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.
CpG岛通常包含基因启动子或外显子，在正常细胞中通常是未甲基化的。CpG岛的甲基化与复制延迟、染色质浓缩以及转录起始抑制有关。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，并且聚焦于基因组中估计的45000个CpG岛中不到15个。在此我们报告使用限制性地标基因组扫描（RLGS）对98例原发性人类肿瘤中每例的1184个未选择的CpG岛的甲基化状态进行的全局分析。我们估计，基因组中45000个CpG岛平均有600个（范围为0至4500个）在肿瘤中发生了异常甲基化，包括早期肿瘤。我们确定了每种肿瘤类型中共同的CpG岛甲基化模式，以及显示出不同肿瘤类型特异性的模式和靶点。在培养的肿瘤细胞中，许多这些基因的表达通过实验性去甲基化得以重新激活。因此，特定CpG岛亚群的甲基化可能对特定肿瘤类型产生影响。
