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Gene panel based prediction of homologous recombination deficiency in breast cancers

Research Project

Project/Area Number 20K23183
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0908:Society medicine, nursing, and related fields
Research InstitutionNational 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)

Project Period (FY) 2020-09-11 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords相同組換え欠損 / 乳がん / 遺伝医療
Outline of Research at the Start

乳がんのPARP阻害剤の適応は胚細胞系列のBRCA1/2遺伝子変異症例に限定されている。そこで体細胞レベルの相同組換え欠損(HRD)に着目するが、HRDスコア測定には腫瘍組織の網羅的遺伝子解析が必要であり、臨床現場に導入可能なより簡便な測定方法が求められる。申請者らはHRDをわずか4つの遺伝子変異・病理学的特徴の組み合わせで推定できることを示してきた。シンプルな予測モデルのため、遺伝子変異情報は全て血液中のゲノムDNAもしくはセルフリーDNAにて測定可能と考える。本研究は、血液中の遺伝子変異情報と病理診断に基づく、採血による新規HRD予測モデルの開発を目標とする。

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.

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。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (1 results)

All 2020

All Presentation (1 results)

  • [Presentation] 若年性乳がんにおける相同組換え欠損の推定モデルの構築2020

    • Author(s)
      渡辺智子、本多隆行、吉田正行、谷岡真樹、白石航也、新井恵吏、牛尼美年子、田村研治、吉田輝彦、金井弥栄、河野隆志
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Research-status Report

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Published: 2020-09-29   Modified: 2023-01-30  

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