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Helicobacter pylori-infection-associated CpG island hypermethylation in the stomach and its possible association with Polycomb repressive marks

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Abstract

Helicobacter pylori infection can induce CpG island (CGI) hypermethylation in gastric mucosa. Recently, genes occupied by Polycomb proteins in embryonic stem cells were shown to be vulnerable to aberrant DNA hypermethylation in cancers. To explore the relationship between H. pylori infection and DNA methylation changes in neoplastic and non-neoplastic stomach, we analyzed 25 CGIs and repetitive DNA elements from 82 chronic gastritis and 69 gastric carcinomas. Twenty-three CGIs showed significantly higher methylation levels in H. pylori-negative gastric carcinoma (n = 28) than in H. pylori-negative chronic gastritis (n = 39; P < 0.05), indicating cancer-associated methylation. Eight CGIs exhibited significantly higher methylation levels in H. pylori-positive chronic gastritis (n = 43) than in H. pylori-negative chronic gastritis (n = 39; P < 0.05). Six CGIs showed both cancer-associated and H. pylori-associated hypermethylation. Six (75%) of the eight H. pylori-associated hypermethylated genes contained at least one of three repressive marks (Suz12 occupancy, Eed occupancy, histone H3 K27 trimethylation), whereas 31% of the remaining cancer-associated hypermethylated genes had at least one mark. The findings suggest that H. pylori infection strongly induces CGI hypermethylation in gastric epithelial cells and that susceptibility to H. pylori-induced DNA hypermethylation may be determined by Polycomb repressive marks in stem or progenitor cells.

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Conflict of interest statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea

    Eun Joo Yoo, Nam-Yun Cho & Gyeong Hoon Kang

  2. Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, South Korea

    Seog-Yun Park, Hye Seung Lee & Gyeong Hoon Kang

  3. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea

    Nayoung Kim

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  1. Eun Joo Yoo
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Correspondence to Gyeong Hoon Kang.

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Supported by the Korea Research Foundation Grant (MOEHRD; KRF-2005-041-E00081; G.H.K.) and by the second stage Brain Korea 21 Project.

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Yoo, E.J., Park, SY., Cho, NY. et al. Helicobacter pylori-infection-associated CpG island hypermethylation in the stomach and its possible association with Polycomb repressive marks. Virchows Arch 452, 515–524 (2008). https://doi.org/10.1007/s00428-008-0596-7

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  • DOI: https://doi.org/10.1007/s00428-008-0596-7

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