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Prediction of timing of driver mutation and distant metastasis in lung adenocarcinoma

Research Project

Project/Area Number 18K19594
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
Research InstitutionNational Cancer Center Japan

Principal Investigator

Kohno Takashi  国立研究開発法人国立がん研究センター, 研究所, 分野長 (80280783)

Co-Investigator(Kenkyū-buntansha) 波江野 洋  東京大学, 大学院新領域創成科学研究科, 特任准教授 (70706754)
Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywordsがん / 遺伝子 / 治療標的 / 発がん / 癌 / ゲノム / 遺伝学 / 病理学
Outline of Final Research Achievements

Information on genetic heterogeneity between primary and metastatic tumors in a lung cancer patient was subjected to mathematical modeling to deduce the timing of driver mutation and distant metastasis. Whole exome sequencing data of fourteen pairs of primary and metastatic lung tumors were obtained and used to identify somatic mutations shared by both tumors and those specific for the primary or metastatic lung tumors in each patient. The data coupled with factors reflecting tumor proliferation rates, which were estimated from sequential data of Computed Tomography (CT) examination, enabled the establishment of a prototype model. According to this model, the timing of driver mutation and distant metastasis was indicated to widely vary among cases. The information would be a basis for precision prevention and therapy of lung cancer and would also generate a new area of cancer study translating mathematical modeling in to the clinic.

Academic Significance and Societal Importance of the Research Achievements

「実際の患者ではどのタイミングでドライバー変異が生じたのか?」の情報が本邦集団で得られたならば、がんの予防をいつから行うことが有効であるかというストラテジーに直結する。また、「実際の患者ではどのタイミングで致死的な転移が生じたのか?」の情報が得られたならば、がんの根治的外科的手術のやり方やその後の治療ストラテジーの改良に資することができる。本研究の成果は、がんの予防や外科的根治治療の精密化の根源となるデータであり、同時に、数理学的モデリングに基づくがんの予防・治療という新たな研究領域の創出につながると期待する。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (8 results)

All 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (2 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Int'l Joint Research] The CRICK Institute(英国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] REToma: a cancer subtype with a shared driver oncogene2020

    • Author(s)
      Kohno T, Tabata J, Nakaoku T.
    • Journal Title

      Carcinogenesis

      Volume: in press Issue: 2 Pages: 123-129

    • DOI

      10.1093/carcin/bgz184

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Next-Generation sequencer analysis of pulmonary pleomorphic carcinoma with a CD74-ROS1 fusion successfully treated with crizotinib2019

    • Author(s)
      Mizuno T, Fujiwara Y*, Yoshida K, Kohno T, Ohe Y.
    • Journal Title

      J Thorac Oncol

      Volume: 14 Issue: 5 Pages: e106-e108

    • DOI

      10.1016/j.jtho.2019.01.005

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Radiopathologic correlation of collision lung cancer with ground-glass opacity2018

    • Author(s)
      Uchida Shinsuke、Tsuta Koji、Kusumoto Masahiko、Shiraishi Kouya、Kohno Takashi、Watanabe Shun-ichi
    • Journal Title

      Asian Cardiovascular and Thoracic Annals

      Volume: 27 Issue: 1 Pages: 45-48

    • DOI

      10.1177/0218492318811549

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Genomic profiling in advanced stage non-small-cell lung cancer patients with platinum-based chemotherapy identifies germline variants with prognostic value in SMYD22018

    • Author(s)
      Galv?n-Femen?a Iv?n、Guindo Marta、Duran Xavier、Calabuig-Fari?as S?lvia、Mercader Josep Maria、Ramirez Jose Luis、Rosell Rafael、Torrents David、Carreras Anna、Kohno Takashi、Jantus-Lewintre Eloisa、Camps Carlos、Perucho Manuel、Sumoy Lauro、Yokota Jun、de Cid Rafael
    • Journal Title

      Cancer Treatment and Research Communications

      Volume: 15 Pages: 21-31

    • DOI

      10.1016/j.ctarc.2018.02.003

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating cell-free plasma tumour DNA shows a higher incidence of EGFR mutations in patients with extrathoracic disease progression2018

    • Author(s)
      Seki Yoshitaka、Fujiwara Yutaka、Kohno Takashi、Yoshida Kazushi、Goto Yasushi、Horinouchi Hidehito、Kanda Shintaro、Nokihara Hiroshi、Yamamoto Noboru、Kuwano Kazuyoshi、Ohe Yuichiro
    • Journal Title

      ESMO open

      Volume: 3 Issue: 2 Pages: e000292-e000292

    • DOI

      10.1136/esmoopen-2017-000292

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] RET fusion and mutation in lung cancer2019

    • Author(s)
      Takashi Kohno
    • Organizer
      RET@CRICK meerting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Genome profile and mutational signature of lung cancer2018

    • Author(s)
      Kohno T
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
    • Invited

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Published: 2018-07-25   Modified: 2021-02-19  

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