PO-008 Accelerated DNA methylation in gastric mucosa adjacent to cancer after HELICOBACTER PYLORI eradication

Abstract

Introduction The molecular irreversibleness with Helicobacter pylori ( H. pylori ) infection may have a role in gastric tumorigenesis after H. pylori eradication. We performed comprehensive DNA methylation profiling of gastric mucosa after H. pylori eradication with or without gastric cancer. Material and methods Four different groups of biopsies including gastric body from subjects without history of H. pylori infection (Hp-: n=23), gastric body from cancer-free subjects after H. pylori eradication (cancer-free body: n=48), gastric body from early gastric cancer patients diagnosed after H. pylori eradication (EGC body: n=42) and its paired samples from adjacent mucosa of cancerous area (EGC ADJ: n=43) were used for the study. Methylation status of five candidate genes ( MYOD1 , SLC16A12 , IGF2 , RORA and PRDM5 ) was examined by the bisulfite pyrosequencing. An Infinium Methylation EPIC BeadChip array was used to characterise the methylation status of >8 50 000 CpG sites for 11 samples. Results and discussions The EGC ADJ group showed highest mean Z score methylation of 5 candidate genes among the four groups of biopsies. In the gastric body (cancer-free body +EGC body), mean Z score methylation was significantly decreased in patients with longer period after eradication, while such association was not observed in EGC ADJ group. Hyper methylated samples were associated with shorter telomere, an indicator for rapid cell turnover, and higher DNMT1 protein expression, an enzyme related to methyl transfer reaction. The genome-wide methylation analysis demonstrated accelerated methylation especially at CpG islands in the EGC ADJ group. Exclusively hypermethylated promoter CpG islands in the same group frequently coded zinc finger proteins. Conclusion Accelerated DNA methylation is associated with molecular irreversibleness and gastric carcinogenesis after H. pylori eradication.