Identification of driver gene mutations in radiation-induced mammary carcinomas

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K00562
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: National Institutes for Quantum and Radiological Science and Technology
• Principal Investigator: Daino Kazuhiro 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 放射線影響研究部, 研究統括(定常) (90543299)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 放射線 / ガンマ線 / 中性子線 / 乳癌 / サブタイプ / 遺伝子変異 / 次世代シーケンス

Outline of Final Research Achievements

In the present study, we classified rat mammary carcinomas developed spontaneously or after exposure to neutrons and gamma-rays into luminal and non-luminal subtypes by immunohistochemistry. We then performed whole-exome sequencing to explore gene mutations in the tumors. Radiation-induced development of hormone receptor-positive mammary carcinomas was suggested by the immunohistochemical classification. The whole-exome sequencing identified somatic mutations in genes involved in DNA repair, cell growth, transcriptional regulation, and several signaling pathways, including Mapk, Pi3k/Akt, and Wnt, in the carcinomas. In addition, focal DNA copy number losses in the tumor suppressor genes were frequently observed in the carcinomas developed after radiation exposure.

Free Research Field

放射線生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により得られた成果は、放射線被ばくによる発がんリスクを説明する分子メカニズムの解明や予防法の開発に有用である。また、照射群に生じた乳がんに特徴的なゲノム異常は、放射線で誘発されたがんの分子指標として発がんリスクの推定に役立つと考えられるため、今後さらなる解析を進める必要がある。