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Establishment of monitoring method using cfDNA gene mutation profile in patients with malignant tumors

Research Project

Project/Area Number 19K07727
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionKanazawa University

Principal Investigator

Kimura Hideharu  金沢大学, 附属病院, 講師 (40444202)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordscfDNA / 非小細胞肺癌 / 血中遊離DNA / 肺癌
Outline of Research at the Start

本研究では、以下の項目を進め、目的に対する結果を示す。
①cfDNAと腫瘍組織から遺伝子変異プロファイルを作成する。
②cfDNAは病変臓器間のヘテロ不均一性をカバーできることを示す。
③cfDNAは治療経過中に変動する遺伝子プロファイルを捉えることを示す。
④cfDNAは転移出現予測マーカーとなりうることを示す。

Outline of Final Research Achievements

A total of 114 cfDNA samples at diagnosis and resistance to treatment were collected from 42 patients with advanced non-small cell lung cancer, and cfDNA was extracted. A gene mutation profile was created using the recovered cfDNA. We published a paper on the results of analysis of gene mutation mutation profiles using autopsy tissues (Koba H, Kimura H et al. Sci Rep. 2021). In the paper, it was shown that cfDNA is enriched with important gene mutations that characterize malignant tumors, and that the gene mutation profile in cfDNA changes over the course of treatment. These results suggest that cfDNA may better reflect the characteristics of the entire tumor compared to tumor tissue.

Academic Significance and Societal Importance of the Research Achievements

cfDNA遺伝子検査は、腫瘍組織の代替試料というだけではなく、腫瘍の特性や変動する臨床事象を捉えるために腫瘍組織より適した試料となりうることを示した。これまでにcfDNAがもつ試料としての優位性からcfDNA遺伝子変異プロファイル変化を示した研究報告はない。cfDNA遺伝子変異プロファイルの定量変化は、実用的な臨床的バイオマーカーとして有用であり、さらには新たな治療標的の同定やその治療薬の開発に結びつくことが期待できる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (9 results)

All 2021 2020 2019

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 4 results) Presentation (2 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Molecular features of tumor-derived genetic alterations in circulating cell-free DNA in virtue of autopsy analysis2021

    • Author(s)
      Koba Hayato、Kimura Hideharu、Yoneda Taro、Sone Takashi、Ohkura Noriyuki、Hara Johsuke、Hosomichi Kazuyoshi、Tajima Atsushi、Kasahara Kazuo
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 8398-8398

    • DOI

      10.1038/s41598-021-87094-1

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Late-onset programmed cell death protein-1 inhibitor-induced pneumonitis after cessation of nivolumab or pembrolizumab in patients with advanced non-small cell lung cancer: a case series2021

    • Author(s)
      Kimura Hideharu、Sone Takashi、Araya Tomoyuki、Murata Akari、Yamamura Kenta、Ohkura Noriyuki、Hara Johsuke、Abo Miki、Kasahara Kazuo
    • Journal Title

      Translational Lung Cancer Research

      Volume: 10 Issue: 3 Pages: 1576-1581

    • DOI

      10.21037/tlcr-20-582

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful Treatment of Advanced Thymic Carcinoma with Carboplatin plus <b><i>nab</i></b>-Paclitaxel and Maintenance Monotherapy with <b><i>nab</i></b>-Paclitaxel: Two Case Reports2020

    • Author(s)
      Araya Tomoyuki、Kita Toshiyuki、Matsuoka Hiroki、Sakai Tamami、Kimura Hideharu、Kasahara Kazuo
    • Journal Title

      Case Reports in Oncology

      Volume: 13 Issue: 3 Pages: 1506-1512

    • DOI

      10.1159/000510894

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Severe coronavirus disease 2019 (COVID‐19) pneumonia patients treated successfully with a combination of lopinavir/ritonavir plus favipiravir: Case series2020

    • Author(s)
      Koba Hayato、Yoneda Taro、Kaneda Tomoya、Ueda Tsukasa、Kimura Hideharu、Kasahara Kazuo
    • Journal Title

      Clinical Case Reports

      Volume: 8 Issue: 12 Pages: 3143-3148

    • DOI

      10.1002/ccr3.3358

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Real-World Efficacy of First-Line Pembrolizumab in Patients With Advanced or Recurrent Non?Small-Cell Lung Cancer and High PD-L1 Tumor Expression2020

    • Author(s)
      Tambo Yuichi、Sone Takashi、Shibata Kazuhiko、Nishi Kouichi、Shirasaki Hiroki、Yoneda Taro、Araya Tomoyuki、Kase Kazumasa、Nishikawa Shingo、Kimura Hideharu、Kasahara Kazuo
    • Journal Title

      Clinical Lung Cancer

      Volume: XX Issue: 5 Pages: 1-4

    • DOI

      10.1016/j.cllc.2020.02.017

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] A case of EGFR mutation-positive lung adenocarcinoma in which the T790M allele fraction was increased by repeated EGFR-TKI treatment.2019

    • Author(s)
      Kimura H, Amino Y, Koba H, Tambo Y, Ohkura N, Hara J, Sone T, Kasahara K.
    • Journal Title

      Cancer Commun (Lond).

      Volume: 39 Issue: 1 Pages: 67-67

    • DOI

      10.1186/s40880-019-0413-5

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Long-lasting responses after discontinuation of nivolumab treatment for reasons other than tumor progression in patients with previously treated, advanced non-small cell lung cancer.2019

    • Author(s)
      Kimura H, Araya T, Yoneda T, Shirasaki H, Kurokawa K, Sakai T, Koba H, Tambo Y, Nishikawa S, Sone T, Kasahara K.
    • Journal Title

      Cancer Commun (Lond).

      Volume: 39 Issue: 1 Pages: 78-78

    • DOI

      10.1186/s40880-019-0423-3

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] Detection of tumor-associated gene mutations in cell-free DNA of early-stage non-small cell lung cancer patients.2019

    • Author(s)
      Kimura H,Koba H, Kasahara K.
    • Organizer
      11th International Symposium on Circulating Nucleic Acids in Plasma and Serum (CNAPS)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Molecular genetic characteristics of tumor-derived gene alterations in cfDNA.2019

    • Author(s)
      Kimura H,Koba H, Kasahara K.
    • Organizer
      11th International Symposium on Circulating Nucleic Acids in Plasma and Serum (CNAPS)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2023-01-30  

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