Suppression of hepatocarcinogeneis based on the elucidation of HBV integration and epigenome alterations analyzed by G-NaVI

• Project/Area Number: 15H04304
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Itoh Fumio 聖マリアンナ医科大学, 医学部, 教授 (90223180)
• Co-Investigator(Kenkyū-buntansha): 山本 博幸 聖マリアンナ医科大学, 医学部, 准教授 (40332910) ; 渡邊 嘉行 聖マリアンナ医科大学, 医学部, 講師 (90329243)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000); Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
• Keywords: エピゲノム / HBV / 肝癌 / DNA組み込み / DNAメチル化

Outline of Final Research Achievements

Integration of DNA viruses into the human genome plays an important role in various types of tumors, including hepatitis B virus (HBV)-related hepatocellular carcinoma. To gain clearer insights into the roles of HBV DNA integration in HCC, we have characterized the molecular details and clinical impact of HBV integration on the epigenomes of human cells and HBV. We have also successfully developed a single-molecule, real-time sequencing-based method for structural analysis of integrated HBV genomes. The observed dynamic changes in DNA methylation of the host and viral genomes as well as genetic and epigenetic alterations in HCC may functionally affect the biological behavior of HBV-related HCC.

Research Products

• [Presentation] Epigenetic alteration at HBV integrants is associated with methylation at flanking human genome (2017)
  • Author(s): 渡邊嘉行、及川律子、山本博幸、伊東文生
  • Organizer: The 107th Annual Meeting of the American Association for Cancer Research
  • Int'l Joint Research
• [Presentation] NGS解析を応用した宿主側及びHBV側要因からみた肝臓がん組み込み部位とメチル化異常の検討 (2017)
  • Author(s): 渡邊嘉行、及川律子、山本博幸、四柳 宏、伊東文生
  • Organizer: 第114回日本内科学会総会・講演会
• [Presentation] がんゲノム解析の臨床応用と個別化・先制医療への展開 (2016)
  • Author(s): 山本博幸
  • Organizer: 第53回日本臨床分子医学会学術集会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
  • Invited
• [Presentation] 次世代シークエンサーによるB型肝炎ウイルスDNA全組み込み解析に基づく発癌機構解明 (2016)
  • Author(s): 山本博幸、渡邊嘉行、及川律子、山本雅一、國土典宏、田中真二、有井滋樹、四柳宏、小池和彦、伊東文生
  • Organizer: 第53回日本臨床分子医学会学術集会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
• [Presentation] A Next-Generation Sequencing-based G-NaVI Method Revealed that DNA Methylation in the Integrated HBV Genome is Related to the Methylation Status of the Integration Sites within the Human Genome (2016)
  • Author(s): 山本博幸、渡邊嘉行、及川律子、渡邊綱正、四柳宏、伊東文生
  • Organizer: DDW2016
  • Place of Presentation: San Diego (U.S.A.)
  • Int'l Joint Research
• [Presentation] G-NAVI 法による宿主側及びHBV 側要因からみた組み込み部位とメチル化異常の検討 (2016)
  • Author(s): 渡邊嘉行、及川律子、山本博幸、四柳宏、伊東文生
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）