Genomic analysis of circulating cell-free DNA to achieve precision medicine for advanced urological cancers
| Project/Area Number |
17H04327
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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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| Research Field |
Urology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| 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)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(15 results)
