5' CPG ISLAND METHYLATION IS ASSOCIATED WITH TRANSCRIPTIONAL SILENCING OF THE TUMOR-SUPPRESSOR P16/CDKN2/MTS1 IN HUMAN CANCERS
5' CPG ISLAND METHYLATION IS ASSOCIATED WITH TRANSCRIPTIONAL SILENCING OF THE TUMOR-SUPPRESSOR P16/CDKN2/MTS1 IN HUMAN CANCERS
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DOI：
10.1038/nm0795-686
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发表时间：
1995-07-01
期刊：
影响因子：
82.9
通讯作者：
SIDRANSKY, D
中科院分区：
文献类型：
--
作者：
MERLO, A;HERMAN, JG;SIDRANSKY, D
染色体9 p21上的杂合性丢失是人类癌症中最常见的遗传改变之一。p16（该区域的候选抑制基因）的点突变率在9 p21等位基因缺失的大多数原发性肿瘤中较低。具有结构未改变的p16的单体细胞系显示p16的5' CpG岛的甲基化。这种独特的甲基化模式与完全转录阻断相关，该阻断在用5-脱氧氮杂胞苷处理后是可逆的。此外，在大约20%的不同原发性肿瘤中也发现p16的5' CpG岛的从头甲基化，但在正常组织中没有发现，这可能代表了人类癌症中肿瘤抑制基因失活的共同途径。
Loss of heterozygosity on chromosome 9p21 is one of the most frequent genetic: alterations identified in human cancer. The rate of point mutations of p16, a candidate suppressor gene of this area, is low in most primary tumours with allelic loss of 9p21. Monosomic cell lines with structurally unaltered p16 show methylation of the 5' CpG island of p16. This distinct methylation pattern was associated with a complete transcriptional block that was reversible upon treatment with 5-deoxyazacytidine. Moreover, de novo methylation of the 5' CpG island of p16 was also found in approximately 20% of different primary neoplasms, but not in normal tissues, potentially representing a common pathway of tumour suppressor gene inactivation in human cancers.