PT  - JOURNAL ARTICLE
AU  - M Cravo
AU  - R Pinto
AU  - P Fidalgo
AU  - P Chaves
AU  - L Glória
AU  - C Nobre-Leitão
AU  - F Costa Mira
TI  - Global DNA hypomethylation occurs in the early stages of intestinal type gastric carcinoma.
AID  - 10.1136/gut.39.3.434
DP  - 1996 Sep 01
TA  - Gut
PG  - 434--438
VI  - 39
IP  - 3
4099  - http://gut.bmj.com/content/39/3/434.short
4100  - http://gut.bmj.com/content/39/3/434.full
SO  - Gut1996 Sep 01; 39
AB  - 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 (3H)-S-adenosylmethionine and Sss1 methylase. A higher incorporation of (3H) methyl groups reflects a lower degree of intrinsic methylation. RESULTS: A graduated increase in (3H) 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/micrograms/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.