Global DNA hypomethylation occurs in the early stages of intestinal type gastric carcinoma

Background-Global DNA hypomethylation has been found in the premalignant stages of some neoplasms and has been implicated as an important factor for tumour progression. Aims-The aim of this study was to evaluate whether DNA hypomethylation occurs during the process of gastric carcinogenesis. Methods-Gastric specimens were obtained from 49 patients and histologically classified as: normal 10, superficial gastritis 14, chronic atrophic gastritis with intestinal metaplasia 15, and intestinal type of gastric carcinoma 10. Global DNA methylation was assessed by incubating DNA with (H-3)-S-adenosylmethionine and Sss1 methylase. A higher incorporation of (H-3) methyl groups reflects a lower degree of intrinsic methylation. Results-A graduated increase in (H-3) methyl group incorporation into DNA was found over the range extending from normal gastric mucosa, to superficial gastritis and to chronic atrophic gastritis (136 556 (24 085) v 235 725 (38 636) v 400 998 (26 747 dpm/mu g/DNA respectively; p=0.0002). No further increase was found in specimens from patients with carcinoma. No differences were found between extent of DNA methylation in neoplastic or non-neoplastic mucosa from patients with gastric carcinoma. Hypomethylation of DNA increased substantially with severe atrophy (p=0.01) or with type III intestinal metaplasia (p=0.15). Conclusions-Global DNA hypomethylation occurs in the early stages of gastric carcinogenesis, and it may be a novel biomarker of gastric neoplasia, useful in monitoring the response to chemopreventive agents.