| Research Abstract |
To assess the physiological consequence and clinical significance of gene promoter methylation in gastric epithelia, our laboratory has been studied the methylation status of tumor suppressor and tumor-related genes, including APC, DAP-kinase, DCC, E-cadherin, GSTP1, hMLH1, p16, PTEN, RASSF1A, RUNX3 and TSLC1, in neoplastic and nonneoplastic gastric epithelia. The tumor suppressor and tumor-related genes, except APC, were generally unmethylated in nonneoplastic gastric epithelia obtained from younger individuals. The frequencies of methylation increased with age to varying degrees in various genes, although GSTP1 and PTEN methylation was completely absent in both neoplastic and nonneoplastic gastric epithelia. The methylation frequencies in each gene were found to be comparable in neoplastic and nonneoplastic gastric epithelia, except the methylation of RUNX3 and TSLC1, which was mostly cancer-specific (P0x<0.01). When methylation frequencies were compared between nonneoplastic gastric epithelia from cancer-bearing and non-cancer-bearing stomachs, hMLH1 and p16 methylation was more frequent in those from cancer-bearing stomachs (P0<0.01). Promoter methylation in tumor suppressor and tumor-related genes initially occurs in nonneoplastic gastric epithelia, increases with age, and ultimately silences gene function to constitute a field-defect that may predispose tissues to gastric cancer evolution. In clinical applications RUNX3 and TSLC1 methylation may be utilized as molecular diagnostic markers, and hMLH1 and p16 methylation as predictors of malignancy in the stomach.
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