DNA methylation accumulation in gastric mucosa adjacent to cancer after Helicobacter pylori eradication

Sayumi Tahara, Tomomitsu Tahara, Noriyuki Horiguchi, Takema Kato, Yasuko Shinkai, Hiromi Yamashita, Hyuga Yamada, Tomohiko Kawamura, Tsuyoshi Terada, Masaaki Okubo, Mitsuo Nagasaka, Yoshihito Nakagawa, Tomoyuki Shibata, Seiji Yamada, Makoto Urano, Tetsuya Tsukamoto, Hiroki Kurahashi, Makoto Kuroda, Naoki Omiya

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)80-88
Number of pages9
JournalInternational Journal of Cancer
Volume144
Issue number1
DOIs
Publication statusPublished - 01-01-2019

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DNA Methylation
Gastric Mucosa
Helicobacter pylori
Methylation
Stomach
Neoplasms
Stomach Neoplasms
CpG Islands
Helicobacter Infections
Carcinogenesis
Biopsy
DNA Fingerprinting
Zinc Fingers
Telomere
Genes
Mucous Membrane
Proteins
Genome
Enzymes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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 ; Omiya, Naoki. / DNA methylation accumulation in gastric mucosa adjacent to cancer after Helicobacter pylori eradication. In: International Journal of Cancer. 2019 ; Vol. 144, No. 1. pp. 80-88.
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Tahara, S, Tahara, T, Horiguchi, N, Kato, T, Shinkai, Y, Yamashita, H, Yamada, H, Kawamura, T, Terada, T, Okubo, M, Nagasaka, M, Nakagawa, Y, Shibata, T, Yamada, S, Urano, M, Tsukamoto, T, Kurahashi, H, Kuroda, M & Omiya, N 2019, 'DNA methylation accumulation in gastric mucosa adjacent to cancer after Helicobacter pylori eradication', International Journal of Cancer, vol. 144, no. 1, pp. 80-88. https://doi.org/10.1002/ijc.31667

DNA methylation accumulation in gastric mucosa adjacent to cancer after Helicobacter pylori eradication. / 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; Omiya, Naoki.

In: International Journal of Cancer, Vol. 144, No. 1, 01.01.2019, p. 80-88.

Research output: Contribution to journalArticle

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T1 - DNA methylation accumulation in gastric mucosa adjacent to cancer after Helicobacter pylori eradication

AU - Tahara, Sayumi

AU - Tahara, Tomomitsu

AU - Horiguchi, Noriyuki

AU - Kato, Takema

AU - Shinkai, Yasuko

AU - Yamashita, Hiromi

AU - Yamada, Hyuga

AU - Kawamura, Tomohiko

AU - Terada, Tsuyoshi

AU - Okubo, Masaaki

AU - Nagasaka, Mitsuo

AU - Nakagawa, Yoshihito

AU - Shibata, Tomoyuki

AU - Yamada, Seiji

AU - Urano, Makoto

AU - Tsukamoto, Tetsuya

AU - Kurahashi, Hiroki

AU - Kuroda, Makoto

AU - Omiya, Naoki

PY - 2019/1/1

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N2 - 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.

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