Comprehensive DNA methylation analysis in the close interaction between Epstein-Barr virus and host cell

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790347
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Chiba University (2013); The University of Tokyo (2012)
• Principal Investigator: MATSUSAKA Keisuke 千葉大学, 医学(系)研究科(研究院), 助教 (40610150)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: エピジェネティクス / ウイルス学 / 病理学

Research Abstract

Gastric cancers (GCs) have a characteristic subgroup with Epstein-Barr virus (EBV) latent infection. EBV-positive (EBV(+)) GC showed extremely higher methylation phenotype and EBV infection induced genome-wide de novo DNA methylation in a low-methylation cell line, MKN7, resulting in acquisition of EBV(+) particular phenotype. In this study, we tried to clarify the mechanism to induce de novo DNA methylation through time-series analysis of DNA methylation focusing on both host cell and virus. As a result, the EBV genome methylation preceded to the host cellular genome methylation, which implied that there should be well-ordered mechanism through close interaction between EBV and host cells. Host cellular genome-wide methylation completed in only 4 weeks. This study might lead to breakthrough about the mechanism of induction of aberrant DNA methylation.

Research Products

• [Journal Article] DNA methylation in gastric cancer, related to Helicobacter pylori and Epstein - Barr virus (2014)
  • Author(s): ①Matsusaka K, Funata S, Fukayama M, Kaneda A
  • Journal Title: World Journal of Gastroenterology Volume: 20(14) Pages: 3916-3926
  • DOI: 10.3748/wjg.v20.i14.3916.
  • Peer Reviewed
• [Presentation] Epstein - Barr virus infection induces global DNA methylation in gastric cells (2014)
  • Author(s): Matsusaka K
  • Organizer: Epstein - Barr virus 50th Anniversary Conference
  • Place of Presentation: Oxford, U.K
  • Year and Date: 20140323-25
• [Presentation] Time - series DNA methylation analysis in gastric cell following Epstein - Barr virus infection (2013)
  • Author(s): Matsusaka K, Funata S, Aburatani H, Fukayama M, Kaneda A
  • Organizer: The 4th JCA - AACR Special Conference
  • Place of Presentation: Tokyo Bay Maihama Hotel Club Resort, Chiba, Japan
  • Year and Date: 20131216-18
• [Presentation] Time - series DNA methylation analysis in gastric cell following Epstein - Barr virus infection (2013)
  • Author(s): Matsusaka K, Funata S, Aburatani H, Fukayama M, Kaneda A
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20131003-05
• [Presentation] DNA methylation alteration of Epstein - Barr virus genome and host cellular genome in EBV infection to gastric cells (2012)
  • Author(s): Matsusaka K, Kaneda A, Funata S, Takada K, Aburatani H, Fukayama M
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 20120919-21
• [Presentation] EBV陽性胃癌におけるDNAメチル化の網羅的解析 (2012)
  • Author(s): 松坂恵介,金田篤志,永江玄太,牛久哲男,宇於崎宏,瀬戸泰之,高田賢藏,油谷浩幸,深山正久
  • Organizer: 第9回EBウイルス研究会
  • Place of Presentation: 米子
  • Year and Date: 2012-07-06
• [Presentation] Epstein - Barr virus関連胃癌及び非関連胃癌におけるARID1A発現消失の臨床病理学的検討 (2012)
  • Author(s): 阿部浩幸,前田大地,日野るみ,大嶽雄也,磯貝まや,牛久綾,松坂恵介,国田朱子,牛久哲男,宇於崎宏,岩崎善毅,立石陽子,比島恒和,石川俊平,深山正久
  • Organizer: 第9回EBウイルス研究会
  • Place of Presentation: 米子
  • Year and Date: 2012-07-06
• [Presentation] Epstein - Barr virus関連胃癌及び非関連胃癌におけるARID1A発現消失の臨床病理学的検討 (2012)
  • Author(s): 阿部浩幸,前田大地,日野るみ,大嶽雄也,磯貝まや,牛久綾,松坂恵介,国田朱子,牛久哲男,宇於崎宏,岩崎善毅,立石陽子,比島恒和,石川俊平,深山正久
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-26
• [Book] 感染症と, 病理からのメッセージ, EBVと胃癌, 病理と臨床 (2013)
  • Author(s): 阿部浩幸,松坂恵介,深山正久
  • Total Pages: 133-137
  • Publisher: 文光堂
• [Book] 成人病と生活習慣病 (2013)
  • Author(s): 松坂恵介,深山正久
  • Total Pages: 1121-1126
  • Publisher: 東京医学社