fundamental research for the development of germline mutation diagnosis enabling preemptive medicine for lung cancer

• Project/Area Number: 17K10799
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Kyorin University
• Principal Investigator: Ohtsuka Kouki 杏林大学, 医学部, 学内講師 (70439165)
• Co-Investigator(Kenkyū-buntansha): 渡邊 卓 杏林大学, 医学部, 教授 (00191768) ; 藤原 正親 杏林大学, 医学部, 教授 (20407026) ; 田中 良太 杏林大学, 医学部, 准教授 (40415063) ; 松島 早月 杏林大学, 医学部, その他 (80231596) ; 大西 宏明 杏林大学, 医学部, 教授 (80291326)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 肺がん / EGFR germline変異 / 発がんリスク / 次世代シーケンス / TP53変異 / 予後予測 / 早期発見早期治療 / 先制医療 / 家族性肺癌 / 遺伝性肺癌 / EGFR V843I / EGFR L858R / TP53 R248W / germline変異 / 付加変異 / 家族性肺がん / Germline変異 / in vivo発がん実験 / 発がん実験 / メダカ / ゲノム編集 / 肺癌 / 多発癌 / 重複癌 / がん関連遺伝子 / NGSパネル

Outline of Final Research Achievements

In this study, we investigated a family with multiple lung adenocarcinoma with an oncogenic EGFR V843I germline mutation. The EGFR V843I mutation is the causative genetic risk for this familial lung adenocarcinoma. In addition, next-generation sequencing of cancer-associated genes can help detect additional genetic aberrations, such as TP53 mutations, in cancer tissue from cancer-predisposed cases, providing valuable information for predicting prognosis.

Academic Significance and Societal Importance of the Research Achievements

肺がんにおける発がんリスクgermline変異情報は、発がんリスクを把握して、早期発見・早期治療すれば、長期生存を可能にする肺がんの先制医療に活用できる。また次世代シーケンスはそのような発がんリスク変異を有する肺がんの予後を予測すことを可能にする。

Research Products

• [Journal Article] Use of a plasma test for verifying epidermal growth factor receptor gene (2020)
  • Author(s): Ogura W, Ohtsuka K
  • Journal Title: Respir Med Case Rep Volume: ? Pages: 101007-101007
  • DOI: 10.1016/j.rmcr.2020.101007
  • Peer Reviewed / Open Access
• [Journal Article] Predisposition to lung adenocarcinoma in a family harboring the germline EGFR V843I mutation. (2019)
  • Author(s): Ohtsuka K, Ohnishi H, Fujiwara M, Morii T, Matsushima S, Ogura W, Yamasaki S, Kishino T, Tanaka R, Watanabe T
  • Journal Title: JCO Precision Oncology Volume: - Issue: 3 Pages: 1-4
  • DOI: 10.1200/po.19.00104
  • Peer Reviewed / Open Access
• [Journal Article] APC:T1556fs and STK11 mutations in duodenal adenomas and adenocarcinomas. (2018)
  • Author(s): Kojima Y, Ohtsuka K, Ohnishi H, Abe N, Furuse J, Watanabe T, Sugiyama M.
  • Journal Title: Surg Volume: 48(8) Issue: 8 Pages: 765-772
  • DOI: 10.1007/s00595-018-1649-4
  • Peer Reviewed / Open Access
• [Presentation] RAD50 Germline Variantを有する家族性癌、消化管重複癌の一例 (2020)
  • Author(s): 大塚弘毅
  • Organizer: 日本臨床検査医学会学術集会
• [Presentation] 野生型マウスにおける自然発生がんの検討 (2019)
  • Author(s): 大塚弘毅
  • Organizer: 日本臨床検査医学会総会
• [Presentation] Whole genome sequencing of family members with the germline EGFR V843i mutation predisposed to lung adenocarcinoma (2017)
  • Author(s): Kouki Ohtsuka
  • Organizer: WASPaLM 2017
  • Int'l Joint Research