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Epstein–Barr Virus Infection as an Epigenetic Driver of Tumorigenesis

Atsushi Kaneda, Keisuke Matsusaka, Hiroyuki Aburatani and Masashi Fukayama
Atsushi Kaneda
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Keisuke Matsusaka
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Hiroyuki Aburatani
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Masashi Fukayama
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DOI: 10.1158/0008-5472.CAN-11-3919 Published July 2012
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Abstract

Epstein–Barr virus (EBV) establishes latent infection and is associated with tumors, such as Burkitt lymphoma, nasopharyngeal carcinoma, and gastric cancers. We recently reported that EBV+ gastric cancer shows an EBV+/extensively high-methylation epigenotype, and in vitro EBV infection induces extensive DNA methylation with gene repression within 18 weeks. On the basis of the absence of both EBV and high-methylation accumulation in the surrounding mucosa of EBV+ gastric cancer, it is suggested that an EBV-infected cell acquires extensive methylation to silence multiple tumor suppressor genes in a short time period and transforms into cancer cells, not forming a precancerous field with EBV infection or methylation accumulation. The methylation mechanism induced by EBV infection has not been fully clarified. Differences in EBV genome methylation that are dependent on a different latency status or other epigenomic alterations, such as 3-dimensional conformation and histone modification, may affect host genome methylation. Expressions of viral proteins and small RNAs are also different depending on latency status, and some viral proteins might trigger DNA methylation by inducing DNA methyltransferase overexpression. In this review, we discuss these roles of EBV infection in driving tumorigenesis and their possible association with aberrant DNA methylation. Cancer Res; 72(14); 3445–50. ©2012 AACR.

  • Received December 2, 2011.
  • Revision received February 22, 2012.
  • Accepted March 7, 2012.
  • ©2012 American Association for Cancer Research.
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Cancer Research: 72 (14)
July 2012
Volume 72, Issue 14
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Epstein–Barr Virus Infection as an Epigenetic Driver of Tumorigenesis
Atsushi Kaneda, Keisuke Matsusaka, Hiroyuki Aburatani and Masashi Fukayama
Cancer Res July 15 2012 (72) (14) 3445-3450; DOI: 10.1158/0008-5472.CAN-11-3919

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Epstein–Barr Virus Infection as an Epigenetic Driver of Tumorigenesis
Atsushi Kaneda, Keisuke Matsusaka, Hiroyuki Aburatani and Masashi Fukayama
Cancer Res July 15 2012 (72) (14) 3445-3450; DOI: 10.1158/0008-5472.CAN-11-3919
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  • Article
    • Abstract
    • Introduction
    • DNA Methylation in Gastric Cancer
    • Latent Epstein–Barr Virus Infection
    • Roles of Epstein–Barr Virus Latent Genes
    • MiRNA Encoded by Epstein–Barr Virus
    • MiRNAs of Host Cells
    • Histone Modification
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