2021 Fiscal Year Final Research Report
Identification of radiation-sensitive genes for achieving precision medicine for medical radiation protection
| Project/Area Number |
19H04270
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 63020:Radiation influence-related
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| Research Institution | Hiroshima University |
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Principal Investigator |
Matsuura Shinya 広島大学, 原爆放射線医科学研究所, 教授 (90274133)
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| Co-Investigator(Kenkyū-buntansha) |
宮本 達雄 山口大学, 大学院医学系研究科, 教授 (40452627)
阿久津 シルビア夏子 (AkutsuSilviaNatsuko) 広島大学, 原爆放射線医科学研究所, 助教 (10822299)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 放射線感受性 / 個人差 / ゲノム編集 |
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| Outline of Final Research Achievements |
The human population includes genetically susceptible individuals with radiation sensitivity, and there is concern that such individuals may have an increased risk of cancer upon medical radiation exposure. However, the genetic predisposition has not yet been fully elucidated. In this study, we performed whole-exome sequencing of 29 ovarian cancer patients and detected the NBS1 I171V variant. To clarify whether this variant indeed contributes to chromosomal radiosensitivity, we generated NBS1 I171V variant homozygous knock-in HCT116 cells and mice using the CRISPR/Cas9 system. Radiation-induced micronucleus formation and chromosomal aberration frequency were significantly increased in both HCT116 cells and mouse embryonic fibroblasts with knock-in of the NBS1 I171V variant compared with the levels in wild-type cells. These results suggested that the NBS1 I171V variant might be a genetic factor underlying individual differences in chromosomal radiosensitivity.
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| Free Research Field |
遺伝医学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で、放射線感受性を規定する代表的なNBS1遺伝子のVUS(Variant of Uncertain Significance)について、ヒトモデル細胞とノックインモデルマウスを作成して、放射線感受性を指標にVUSを再分類することに成功した。クリニカルシーケンスで検出される放射線感受性遺伝子のバリアントには病的意義が不明のものが多く、その場合、医学的管理方針の確立は困難である。本研究はそのようなUVSの評価に有用であり、医療放射線防護のプレシジョン・メディシン実現に向けて研究基盤の整備が大きく進むことが期待される。
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