The Overmethylated Genes in Helicobacter Pylori -Infected Gastric Mucosa Are Demethylated in Gastric Cancers

Background The transitional-CpG sites between weakly methylated genes and densely methylated retroelements are overmethylated in the gastric mucosa infected with Helicobacter pylori ( H. pylori ) and they are undermethylated in the gastric cancers depending on the level of loss of heterozygosity (LOH) events. This study delineated the transitional-CpG methylation patterns of CpG-island-containing and -lacking genes in view of the retroelements. Methods The transitional-CpG sites of eight CpG-island-containing genes and six CpG-island-lacking genes were semi-quantitatively examined by performing radioisotope-labelling methylation-specific PCR under stringent conditions. The level of LOH in the gastric cancers was estimated using the 40 microsatellite markers on eight cancer-associated chromosomes. Each gene was scored as overmethylated or undermethylated based on an intermediate level of transitional-CpG methylation common in the H. pylori -negative gastric mucosa. Results The eight CpG-island genes examined were overmethylated depending on the proximity to the nearest retroelement in the H. pylori -positive gastric mucosa. The six CpG-island-lacking genes were similarly methylated in the H. pylori -positive and -negative gastric mucosa. In the gastric cancers, long transitional-CpG segments of the CpG-island genes distant from the retroelements remained overmethylated, whereas the overmethylation of short transitional-CpG segments close to the retroelements was not significant. Both the CpG-island-containing and -lacking genes tended to be decreasingly methylated in a LOH-level-dependent manner. Conclusions The overmethylated genes under the influence of retroelement methylation in the H. pylori -infected stomach are demethylated in the gastric cancers influenced by LOH.