Accumulation of aberrant CpG hypermethylation by Helicobacter pylori infection promotes development and progression of gastric MALT lymphoma

  • Authors:
    • Takami Kondo
    • Takashi Oka
    • Hiaki Sato
    • Yoko Shinnou
    • Kana Washio
    • Masayuki Takano
    • Toshiaki Morito
    • Katsuyoshi Takata
    • Nobuya Ohara
    • Mamoru Ouchida
    • Kenji Shimizu
    • Tadashi Yoshino
  • View Affiliations

  • Published online on: Tuesday, September 1, 2009
  • Pages:547-557 DOI: 10.3892/ijo_00000366
0

Abstract

Aberrant DNA hypermethylation is an important mechanism for the inactivation of tumor-related genes in human tumors. Gastric mucosa-associated lymphoid tissue (MALT) lymphomas arise from Helicobacter pylori-associated chronic gastritis; most patients are H. pylori-positive and eradication therapy is highly effective. In the present study, we used methylation-specific PCR to analyze the DNA methylation status of 11 tumor-related genes (Kip2, p16, hMLH-1, p15, p73, MGMT, DAPK, MINT1, MINT2, MINT31 and HCAD) in 21 specimens of MALT lymphoma, 5 specimens of MALT lymphoma with large cell component (high-grade MALT lymphoma), 15 specimens of diffuse large B-cell lymphoma (DLBCL), 8 specimens of complete remission of MALT lymphoma after eradication therapy, 5 specimens with no evidence of malignancy and PBMCs from 10 healthy donors. The average number of methylated genes was significantly greater in gastric lymphomas as compared to normal controls (P<0.001). The CpG island methylator phenotype (CIMP) was observed in 93.3% (14/15) of DLBCLs, 100% (5/5) of high-grade MALT lymphomas and 61.9% (13/21) of MALT lymphomas; in contrast, CIMP was not found in the control group (0%). The average number of methylated genes and the CIMP incidence significantly increased with H. pylori infection. Furthermore, aberrant CpG methylation of specific genes, such as p16, MGMT and MINT31, was consistently associated with H. pylori infection. These findings strongly suggest that H. pylori infection causes the aberrant DNA hypermethylation of specific genes and induces CIMP, which is an important epigenetic mechanism for the development and progression of gastric MALT lymphoma; additionally, our findings provide new epigenetic markers.

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September 2009
Volume 35 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

2015 Impact Factor: 3.018
Ranked #30/211 Oncology
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APA
Kondo, T., Oka, T., Sato, H., Shinnou, Y., Washio, K., Takano, M. ... Yoshino, T. (2009). Accumulation of aberrant CpG hypermethylation by Helicobacter pylori infection promotes development and progression of gastric MALT lymphoma. International Journal of Oncology, 35, 547-557. http://dx.doi.org/10.3892/ijo_00000366
MLA
Kondo, T., Oka, T., Sato, H., Shinnou, Y., Washio, K., Takano, M., Morito, T., Takata, K., Ohara, N., Ouchida, M., Shimizu, K., Yoshino, T."Accumulation of aberrant CpG hypermethylation by Helicobacter pylori infection promotes development and progression of gastric MALT lymphoma". International Journal of Oncology 35.3 (2009): 547-557.
Chicago
Kondo, T., Oka, T., Sato, H., Shinnou, Y., Washio, K., Takano, M., Morito, T., Takata, K., Ohara, N., Ouchida, M., Shimizu, K., Yoshino, T."Accumulation of aberrant CpG hypermethylation by Helicobacter pylori infection promotes development and progression of gastric MALT lymphoma". International Journal of Oncology 35, no. 3 (2009): 547-557. http://dx.doi.org/10.3892/ijo_00000366