DNA methylation accumulation in gastric mucosa adjacent to cancer after Helicobacter pylori eradication. Issue 1 (12th November 2018)

• Record Type: Journal Article
• Authors: Tahara, Sayumi; Tahara, Tomomitsu; Horiguchi, Noriyuki; Kato, Takema; Shinkai, Yasuko; Yamashita, Hiromi; Yamada, Hyuga; Kawamura, Tomohiko; Terada, Tsuyoshi; Okubo, Masaaki; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Shibata, Tomoyuki; Yamada, Seiji; Urano, Makoto; Tsukamoto, Tetsuya; Kurahashi, Hiroki; Kuroda, Makoto; Ohmiya, Naoki
• Is Part Of: International journal of cancer. Volume 144:Issue 1(2019)
• Page Start: 80
• Page End: 88
• Publication Date: 2018-11-12
• Subjects: Helicobacter pylori -- eradication -- DNA methylation -- molecular irreversibleness -- genome‐wide methylation; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.31667
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Molecular irreversibleness with Helicobacter pylori ( H. pylori ) infection might 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. Using four different groups of biopsies obtained from gastric body without history of H. pylori infection (Hp‐), gastric body without cancer after H. pylori eradication (cancer‐free body), gastric body with early gastric cancer diagnosed after H. pylori eradication (EGC body) and their paired samples from adjacent mucosa of cancer (EGC ADJ), 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 also used to characterize the methylation status of greater than 850, 000 CpG sites. The EGC ADJ group showed highest methylation levels of five candidate genes among the four groups of biopsies. In the gastric body (cancer‐free body + EGC body), methylation levels were 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 strikingly higher methylation levels especially at CpG islands in the EGC ADJ group. Exclusively hypermethylated promoter CpG islands in the same group frequently coded zinc finger proteins. Our data show that DNA methylation accumulation is associated with molecular irreversibleness and gastric carcinogenesis after H. pylori eradication. Abstract : What's new? Molecular irreversibleness caused by Helicobacter pylori infection might play a role in gastric tumorigenesis sometimes observed after successful eradication, but the mechanisms remain unclear. This study documents DNA methylation accumulation in the mucosa adjacent to gastric cancer after H. pylori eradication, supporting the concept that DNA methylation is associated with molecular irreversibleness and gastric carcinogenesis and could help find biomarkers. The discovery of frequently methylated genes that code zinc finger proteins also emphasizes the importance of pathway‐specific molecular changes, and suggests that targeted epigenetic therapies could be useful in the treatment and chemoprevention of gastric cancer after H. pylori eradication.