Melki J R, Vincent P C, Clark S J
Kanematsu Laboratories, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
Cancer Res. 1999 Aug 1;59(15):3730-40.
Hypermethylation in cancer often occurs in CpG islands that span the promoter regions of tumor suppressor genes. However, it is not clear if hypermethylation is limited to single target genes or if multiple genes are simultaneously methylated. To understand the extent of aberrant de novo methylation, we have analyzed the methylation pattern of a number of tumor-related genes in leukemia from the same cohort of patients. We used bisulfite genomic sequencing to characterize the methylation pattern of the CpG islands associated with the calcitonin, estrogen receptor, E-cadherin, p15, p16, Rb, GST-Pi, and HIC1 genes in the bone marrow from 9 normal and 20 patients with acute myeloid leukaemia (AML). All of the normal control samples were essentially unmethylated for each of the eight tumor-related genes studied. In contrast, 19 of 20 (95%) of the AML patients had an abnormal methylation pattern in at least one gene, and 15 of 20 (75%) had abnormal methylation patterns in two or more of the target genes. We conclude that there is a general deregulation of CpG island methylation in leukemia and that hypermethylation is not limited to single genes, but a number of genes are methylated concurrently. Moreover, the subset of genes that are commonly methylated in leukemia appear to be cancer type specific.
癌症中的高甲基化通常发生在跨越肿瘤抑制基因启动子区域的CpG岛中。然而，尚不清楚高甲基化是否仅限于单个靶基因，还是多个基因同时发生甲基化。为了了解异常从头甲基化的程度，我们分析了同一组患者白血病中多个肿瘤相关基因的甲基化模式。我们使用亚硫酸氢盐基因组测序来表征与降钙素、雌激素受体、E-钙黏蛋白、p15、p16、Rb、谷胱甘肽S-转移酶Pi（GST-Pi）和HIC1基因相关的CpG岛在9名正常人和20名急性髓系白血病（AML）患者骨髓中的甲基化模式。在所研究的八个肿瘤相关基因中，所有正常对照样本基本上均未甲基化。相比之下，20名AML患者中有19名（95%）至少在一个基因中存在异常甲基化模式，20名中有15名（75%）在两个或更多靶基因中存在异常甲基化模式。我们得出结论，白血病中存在CpG岛甲基化的普遍失调，并且高甲基化不限于单个基因，而是多个基因同时发生甲基化。此外，白血病中常见甲基化的基因子集似乎具有癌症类型特异性。
