GLOBAL DNA HYPOMETHYLATION OCCURS IN THE EARLY STAGES OF INTESTINAL-TYPE GASTRIC-CARCINOMA

Background-Global DNA hypomethylation has been found in the premaligna nt stages of some neoplasms and has been implicated as an important fa ctor for tumour progression. Aims-The aim of this study was to evaluat e whether DNA hypomethylation occurs during the process of gastric car cinogenesis. 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 intesti nal 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 atrophi c 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 sp ecimens from patients with carcinoma. No differences were found betwee n extent of DNA methylation in neoplastic or non-neoplastic mucosa fro m patients with gastric carcinoma. Hypomethylation of DNA increased su bstantially with severe atrophy (p=0.01) or with type III intestinal m etaplasia (p=0.15). Conclusions-Global DNA hypomethylation occurs in t he early stages of gastric carcinogenesis, and it may be a novel bioma rker of gastric neoplasia, useful in monitoring the response to chemop reventive agents.