2019 Fiscal Year Final Research Report
Mechanisms of carcinogenesis in individuals harboring germline BRCA1/2 pathogenic variants
| Project/Area Number |
18K16292
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | Yamanashi Prefectural Hospital Organization |
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Principal Investigator |
Yosuke Hirotsu 地方独立行政法人山梨県立病院機構山梨県立中央病院(がんセンター局ゲノム解析センター), ゲノム解析センター, チーフ研究員 (10793838)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Keywords | BRCA1/2 / 生殖細胞系列 / 乳癌 / 卵巣癌 / PARP |
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| Outline of Final Research Achievements |
Individuals with germline BRCA1/2 pathogenic mutations have a high-risk of the development of breast, ovarian, and prostate cancers. BRCA1/2 pathological variants are racially diverse. However, it remained systematically unknown the functional significance of BRCA1/2 variants and potential therapeutic targets to PARP inhibitors.
In this study, we examined the BRCA1/2 variants which were previously classified as benign, variants of uncertain significance (VUS) and pathogenic. We assessed these variants using database (MH-BRCA) and redefined some missense variants as likely pathogenic. Furthermore, we could assess whether tumor with these variants have a sensitivity to PARP inhibitor (i.e. olaparib).
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| Free Research Field |
腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果は、VUSの再評価を行うことで、機能的に再分類されること、PARP阻害剤に対する感受性を再評価することの重要性があることを示した。
日本人で同定されるBRCA1/2バリアントに対し、データベースを使って解析をすることで、再評価が可能である考えられる。また、機能的意義が明らかになった癌に対して、ポリADP-リボースポリメラーゼ（PARP）阻害剤に対する感受性を評価することも可能である。
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