Advances in Brief CpG Island Methylation in Premalignant Stages of Gastric Carcinoma1

There are limited reports on methylation analysis of the premalignant lesions of gastric carcinoma thus far. This is despite the fact that gastric carcinoma is one of the tumors with a high frequency of CpG island hypermethylation. To determine the frequency and timing of hypermethy-lation during multistep gastric carcinogenesis, non-neoplastic gastric mu-cosa (n 5 118), adenomas (n 5 61), and carcinomas (n 5 64) were analyzed for their p16, human Mut L homologue 1 (hMLH1), death-associated protein (DAP)-kinase, thromobospondin-1 (THBS1), and tissue inhibitor of metalloproteinase 3 (TIMP-3) methylation status using meth-ylation-specific PCR. Three different classes of methylation behaviors were found in the five tested genes. DAP-kinase was methylated at a similar frequency in all four stages, whereas hMLH1 and p16 were meth-ylated in cancer samples (20.3 % and 42.2%, respectively) more frequently than in intestinal metaplasia (6.3 % and 2.1%, respectively) or adenoma