Mutation sigunature of atomic bomb survivor's cancer tissue

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07463
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Nagasaki University
• Principal Investigator: Akazawa Yuko 長崎大学, 原爆後障害医療研究所, 准教授 (80582113)
• Co-Investigator(Kenkyū-buntansha): 中島 正洋 長崎大学, 原爆後障害医療研究所, 教授 (50284683) ; 柴田 龍弘 国立研究開発法人国立がん研究センター, 研究所, 分野長 (90311414)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: atomic bomb / survivor / mutation signature / radiation / DNA damage

Outline of Final Research Achievements

We aimed to perform whole-genome analysis and signature analysis using next-generation sequencers to identify characteristic structural variations and mutation signatures specific to cancer among atomic bomb (A-bomb) survivors. We have already initiated a pilot study on 20 cases of close-range exposure (13 lung cancer cases and 7 thyroid cancer cases), and confirmed the feasibility of analyzing DNA quality in thyroid cancer and lung cancer of cases with very close-range exposure. We found no significant differences in the number or types of structural variants larger than 50 base pairs between close-range and distant-range exposed individuals. Fusion genes, including RET-PTC, which were observed in the aftermath of the Chernobyl accident, were not prominent in A-bomb survivors. However, we discovered a new fusion gene that has not been reported before in thyroid cancer among individuals with close-range A-bomb exposure patients. We are currently conducting further signature analysis.

Free Research Field

病理学

Academic Significance and Societal Importance of the Research Achievements

原爆による放射線被ばくによる発がんのマーカーがゲノム内に検出できれば、集団の中で疫学的にしか明らかではなかった原爆被ばく者の発がんリスクが、個々の症例レベルで分子遺伝学的に放射線誘発性を同定することが可能になる。放射線の医療利用による発がんを含め、被ばく後長期的な発がんのリスク予測など社会的重要性は大きく、放射線防護基準に影響を与える可能性がある。