DNA HYPERMETHYLATION AT THE D17S5 LOCUS IS ASSOCIATED WITH GASTRIC CARCINOGENESIS

The aim of this study was to elucidate the significance of aberrant DN A methylation in gastric carcinogenesis. The DNA methylation status at the D17S5 locus, at which a candidate tumor suppressor gene, HIC-1, w as identified, of gastric cancers and non-cancerous gastric mucosae fr om 42 gastric cancer patients was examined by Southern blotting using a methylation-sensitive restriction enzyme. DNA hypermethylation was o bserved in 15, 13, 25 and 45% of the tissues showing no remark able hi stological findings, chronic gastritis without intestinal metaplasia, intestinal metaplasia and gastric cancer, respectively. The incidence of DNA hypermethylation was significantly higher in gastric cancers th an in non-cancerous gastric mucosae (P < 0.05). DNA hypermethylation w as often accompanied by allelic loss at the same locus in gastric canc ers. DNA hypermethylation at the D17S5 locus, which was even detected in precancerous conditions, including intestinal metaplasia, may play a role in gastric carcinogenesis. (C) 1998 Elsevier Science Ireland Lt d.