DNA Methylation Changes in Multistep Gastric Carcinogenesis and Their Relationship with H. pylori Infection and Association of Gastric Cancer
SY Park, N Kim, EJ Yoo, NY Cho, GH Kang. National Cancer Center, Koyang, Republic of Korea; Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
Background: CpG island hypermethylation and genomic DNA hypomethylation are found not only in gastric cancer but also in its premalignant lesions. Helicobacter pylori infection induces aberrant CpG island hypermethylation in gastric mucosae. However, little is known about the relationship between H. pylori infection and aberrant methylation changes in premalignant lesions. The present study aimed to characterize methylation changes of a subset of genes and repetitive DNA elements and their relationship with H. pylori infection in premalignant lesions of gastric cancer.
Design: We performed MethyLight analysis of 25 genes and SAT2 and COBRA analysis of LINE-1 and ALU in a total of 200 gastric tissue samples. H. pylori infection was closely associated with enhanced hypermethylation of CpG island loci in chronic gastritis but this association was not found in intestinal metaplasia, gastric adenoma, and gastric cancer.
Results: H. pylori infection was closely associated with enhanced hypermethylation of CpG island loci in chronic gastritis but this association was not found in intestinal metaplasia, gastric adenoma, and gastric cancer. Intestinal metaplasia and gastric adenoma showed higher number of methylated genes than chronic gastritis regardless of H. pylori infection. Different methylation behaviours depending on types of genes or repetitive DNA elements were found along multistep gastric carcinogenesis. No difference was noted in the number of methylated genes in chronic gastritis or intestinal metaplasia between gastric cancer patients and non-cancer subjects.
Conclusions: Our findings suggest that CpG island hypermethylation and repetitive DNA hypomethylation tend to be enhanced with progression of the lesion along multistep gastric carcinogenesis although the timing of hypermethylation and hypomethylation is different depending on types of genes or repetitive DNA elements.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 98, Tuesday Afternoon