2021 Fiscal Year Final Research Report
Gene panel based prediction of homologous recombination deficiency in breast cancers
Project/Area Number |
20K23183
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund |
Review Section |
0908:Society medicine, nursing, and related fields
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Research Institution | National Cancer Center Japan |
Principal Investigator |
Watanabe Tomoko 国立研究開発法人国立がん研究センター, 中央病院, 遺伝カウンセラー (10773187)
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Project Period (FY) |
2020-09-11 – 2022-03-31
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Keywords | 相同組換え欠損 / 乳がん / 遺伝医療 |
Outline of Final Research Achievements |
Homologous recombination deficiency (HRD) score, indicating HRD status, is not routinely assessed in the breast oncology clinic, particularly in patients without germline BRCA1/2 mutations. The prediction model of HRD in our previous study comprises BRCA1/2 mutation, somatic TP53 mutation, triple negative subtype, and higher tumor grade. When we confirm the concordance of TP53 mutation between cell-free tumor DNA and tissue DNA, we are able to detect HRD-high (HRD score >=42) tumors based on genetic information from peripheral bloods. As a result of this study, the concordance rate of TP53 mutation between cell-free tumor DNA and tissue DNA was up to 60% (3/5 cases), of which 2 cases were below the limit of detection. Based on this result, it might be difficult to predict HRD using cell-free DNA in breast cancer under current conditions, and future strategies should be re-examined.
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Free Research Field |
がんゲノム
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Academic Significance and Societal Importance of the Research Achievements |
乳がんの体細胞TP53遺伝子変異を血液中Cell-free DNA(cfDNA)で測定できれば、体細胞レベルの相同組換え欠損予測に用いる遺伝子変異情報は全て血液中のゲノムDNAもしくはcfDNAにて測定可能と考える。本研究では乳がんの腫瘍組織解析とcfDNA解析のTP53変異の一致率は60%にとどまったが、乳がん症例において血漿中の腫瘍由来遺伝子変異を検出する際の1つの参考情報となると考えられる。
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