Molecular mechanism for the onset of cervical cancer by analysis of HPV integration and DNA methylation

• Project/Area Number: 26462539
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Suzuki Nao 聖マリアンナ医科大学, 医学部, 教授 (90246356)
• Co-Investigator(Kenkyū-buntansha): 上川 篤志 聖マリアンナ医科大学, 医学部, 研究技術員 (60534253)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 子宮頸がん / ヒトパピローマウイルス / ウイルス組込み / HPV / 子宮頸癌

Outline of Final Research Achievements

Viral integration into the human genome upon infection is an important risk factor for various human malignancies. Human papilloma virus (HPV) integration is a key genetic event in cervical carcinogenesis. We performed a next-generation sequencing-based method for sequencing the HPV DNA integration sites, by high-throughput viral integration detection. We identified 12 HPV integration breakpoints in five cervical cancer cell lines and found variable levels of DNA methylation within the integrated HPV genomes. Our study accurately evaluated HPV integration sites in cervical cancer cells using high-throughput viral integration detection method providing basic evidence for HPV integration-driven cervical carcinogenesis.

Research Products

• [Presentation] 子宮頸がん細胞株のHPV遺伝子E6, E7を標的としたゲノム編集による細胞周期関連因子の変動 (2016)
  • Author(s): 上川篤志、戸澤晃子、横道憲幸、鈴木直
  • Organizer: 第68回 日本産科婦人科学会学術集会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
  • Year and Date: 2016-04-21
• [Presentation] 次世代シーケンス解析を用いた子宮頸がん細胞におけるヒトパピローマウイルス組 込み部位の同定 (2016)
  • Author(s): 戸澤晃子、上川篤志、竹内淳、山中弘之、秦ひろか、近藤亜未、三浦彩子、横道憲幸、大原樹、近藤春裕、鈴木直
  • Organizer: 第68回 日本産科婦人科学会学術集会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
  • Year and Date: 2016-04-21