Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype.
Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype.
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发表时间：
1999-11
期刊：
影响因子：
11.2
通讯作者：
M. Toyota;N. Ahuja;Hiromu Suzuki;F. Itoh;Mutsumi Ohe-Toyota;K. Imai;S. Baylin;J. Issa;J. I
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文献类型：
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作者：
M. Toyota;N. Ahuja;Hiromu Suzuki;F. Itoh;Mutsumi Ohe-Toyota;K. Imai;S. Baylin;J. Issa;J. I
5' CpG岛的异常甲基化被认为在肿瘤抑制基因失活中起重要作用。在结直肠癌中，一组肿瘤的特征是一种被称为CpG岛甲基化表型（CIMP）的高甲基化表型，包括p16和hMLH1等基因的甲基化。为了研究CIMP是否存在于胃癌中，我们使用亚硫酸- pcr检测了56例胃癌中5个新克隆的CpG岛的甲基化状态。56例癌症中有23例（41%）同时存在3个或更多位点的甲基化，这表明这些肿瘤具有高甲基化表型CIMP。CIMP与p16、hMLH1等已知基因的甲基化有显著的一致性；23例CIMP+肿瘤中有16例（70%），12例CIMP中间肿瘤中有1例（8%），21例CIMP-肿瘤中有1例（5%）检测到p16甲基化（P<0.0001）。5例表现微卫星不稳定性的肿瘤中有3例检测到hMLH1基因的甲基化，且这3例均为CIMP+。CIMP表型是胃癌的早期事件，56例中有5例存在于癌旁的正常组织中。这些结果提示CIMP可能是胃癌发生的主要途径之一。
Aberrant methylation of 5' CpG islands is thought to play an important role in the inactivation of tumor suppressor genes in cancer. In colorectal cancer, a group of tumors is characterized by a hypermethylator phenotype termed CpG island methylator phenotype (CIMP), which includes methylation of such genes as p16 and hMLH1. To study whether CIMP is present in gastric cancer, the methylation status of five newly cloned CpG islands was examined in 56 gastric cancers using bisulfite-PCR. Simultaneous methylation of three loci or more was observed in 23 (41%) of 56 cancers, which suggests that these tumors have the hypermethylator phenotype CIMP. There was a significant concordance between CIMP and the methylation of known genes including p16, and hMLH1; methylation of p16 was detected in 16 (70%) of 23 CIMP+ tumors, 1 (8%) of 12 CIMP intermediate tumors, and 1 (5%) of 21 CIMP- tumors (P<0.0001). Methylation of the hMLH1 gene was detected in three of five tumors that showed microsatellite instability, and all three of the cases were CIMP+. The CIMP phenotype is an early event in gastric cancer, being present in the normal tissue adjacent to cancer in 5 of 56 cases. These results suggest that CIMP may be one of the major pathways that contribute to tumorigenesis in gastric cancers.