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Genomic analysis of circulating cell-free DNA to achieve precision medicine for advanced urological cancers

Research Project

Project/Area Number 17H04327
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKyoto University

Principal Investigator

Yamasaki Toshinari  京都大学, 医学研究科, 講師 (00607749)

Co-Investigator(Kenkyū-buntansha) 赤松 秀輔  京都大学, 医学研究科, 助教 (20767248)
小川 修  京都大学, 医学研究科, 教授 (90260611)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2019: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2018: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Keywords前立腺癌 / 腎細胞癌 / cfDNA / 薬剤感受性 / バイオマーカー / CTC / 癌 / 腎癌
Outline of Final Research Achievements

There is a need to develop noninvasive biomarkers to guide treatment. We established a highly sensitive method for analyzing androgen receptor gene (AR) copy numbers and mutations in plasma circulating cell-free DNA (cfDNA) from castration-resistant prostate cancer (CRPC) patients using next-generation sequencer and digital PCR. We also established a method to detect VHL gene mutations in cfDNA from renal cell carcinoma (RCC) patients.
AR aberrations in pretreatment cfDNA from CRPC patients were associated with poor response to abiraterone, a novel anti-androgen receptor agent. We also found that the mutation rate of VHL in cfDNA from RCC patients could depend on the tumor volume.
cfDNA may become a useful predictive biomarker for precision medicine in patients with advanced urological cancers.

Academic Significance and Societal Importance of the Research Achievements

本研究では治療中の進行前立腺癌・腎癌患者から血中遊離DNA(cfDNA)を採取し、次世代シークエンサーとデジタルPCRといった手法を用いて、cfDNAにおける遺伝子異常を解析する方法を確立した。また、経時的にcfDNAを採取することで、治療経過に応じてcfDNAに認められる遺伝子異常やアレル頻度が変化することを明らかにした。また、特定の薬剤の治療効果とcfDNA中の遺伝子異常に関連があることを見出した。これらの研究成果は、進行泌尿器癌における薬剤感受性や病勢を予測するシステムを構築し、各病態に最も適した治療を選択する“プレシジョン医療”の実現に寄与するものと考えられる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (15 results)

All 2020 2019 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (14 results) (of which Int'l Joint Research: 6 results)

  • [Journal Article] Clinical utility of androgen receptor gene aberrations in circulating cell-free DNA as a biomarker for treatment of castration-resistant prostate cancer2019

    • Author(s)
      Sumiyoshi Takayuki、Mizuno Kei、Yamasaki Toshinari、Miyazaki Yu、Makino Yuki、Okasho Kosuke、Li Xin、Utsunomiya Noriaki、Goto Takayuki、Kobayashi Takashi、Terada Naoki、Inoue Takahiro、Kamba Tomomi、Fujimoto Akihiro、Ogawa Osamu、Akamatsu Shusuke
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 4030-4030

    • DOI

      10.1038/s41598-019-40719-y

    • NAID

      120006709427

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 淡明型腎細胞癌における血漿遊離 DNA の VHL 遺伝子変異の検討2020

    • Author(s)
      赤松秀輔
    • Organizer
      第4回リキッドバイオプシー研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 淡明型腎細胞癌における血漿遊離DNA中のVHL遺伝子変異の検討2019

    • Author(s)
      住吉崇幸
    • Organizer
      第107回日本泌尿器科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] The evaluation of VHL gene in circulating cell-free DNA from patients with renal cell carcinoma2019

    • Author(s)
      山崎俊成
    • Organizer
      第50回腎癌研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 去勢抵抗性前立腺癌における血漿遊離DNAのアンドロゲン受容体遺伝子異常のバイオマーカーとしての有用性の検討2019

    • Author(s)
      住吉 崇幸
    • Organizer
      第28回泌尿器分子細胞研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Androgen receptor gene aberrations in circulating cell-free DNA from patients with castration-resistant prostate cancer2018

    • Author(s)
      住吉 崇幸
    • Organizer
      第106回泌尿器科学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Androgen receptor gene aberrations in circulating cell free DNA from Japanese castration resistant prostate cancer patients2018

    • Author(s)
      住吉 崇幸
    • Organizer
      AUA2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Detection of Androgen Receptor Gene Aberrations in Circulating Cell-Free DNA from Japanese Castration-Resistant Prostate Cancer Patients2018

    • Author(s)
      住吉 崇幸
    • Organizer
      38th SIU
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Detection of androgen receptor gene aberrations in circulating cell-free DNA from Japanese castration-resistant prostate cancer patients2018

    • Author(s)
      住吉 崇幸
    • Organizer
      第56回日本癌治療学会学術集会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Comparing sequencing of abiraterone and enzalutamide with pre-docetaxel castration resistant prostate cancer2018

    • Author(s)
      水野 桂
    • Organizer
      Asian Pacific Prostate Society 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 去勢抵抗性前立腺癌における血漿遊離DNA中のアンドロゲン受容体遺伝子変異の解析2018

    • Author(s)
      住吉 崇幸
    • Organizer
      第27回泌尿器科分子・細胞研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Digital PCRを用いた去勢抵抗性前立腺癌における血漿遊離DNAのアンドロゲン受容体遺伝子コピー数の同定2017

    • Author(s)
      住吉 崇幸
    • Organizer
      第105回日本泌尿器科学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Detection of copy number variations of androgen receptor gene in cell-free DNA from castration-resistant prostate cancer by digital PCR2017

    • Author(s)
      住吉 崇幸
    • Organizer
      第34回日韓泌尿器科会議
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dynamic alteration of androgen receptor amplification status detected by ctDNA during treatment of castration-resistant prostate cancer2017

    • Author(s)
      赤松 修輔
    • Organizer
      37th Congress of the SIU
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Digital PCRを用いた去勢抵抗性前立腺癌における血漿遊離DNAのアンドロゲン受容体遺伝子コピー数の同定2017

    • Author(s)
      住吉 崇幸
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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