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Identification of gastric cancer driver mutations by using PDX model

Research Project

Project/Area Number 18K07007
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49020:Human pathology-related
Research InstitutionNational Cancer Center Japan

Principal Investigator

Takeshi Kuwata  国立研究開発法人国立がん研究センター, 東病院, 部門長 (00327321)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords胃癌 / 遺伝子変異 / ドライバー遺伝子 / ゼノグラフト / ゲノム
Outline of Final Research Achievements

To identify the driver alteration in gastric cancer (GC), we compared gene alteration profiles between primary tumor (PT), patient-derived xenograft mode (PDX) and cell lines (CL). For the analyses, we used 34 GC PDX and 24 GC cell line, all established in our instituion. Gnemo profiling analyses revealed total gene mutation (single nucleotide variant [SNV] and insertion/deletion [Indel]) in 47 genes and 7 copy number alteration in 7 genes. The gene 、of which constitutive same alterations (SNV, Indel or CNV) between PT, PDX and CL were observed in all cases, include TP53, KRAS, MYC. We suppose these genes are the driver mutations in gastric cancer and could be the targets of precision oncology.

Academic Significance and Societal Importance of the Research Achievements

本研究では、胃癌について原発巣とヒト患者由来ゼノグラフトモデルおよび細胞株における遺伝子プロファイリングの結果比較より、ドライバー遺伝子の推定・同定が可能となることをしめすことができた。またPDX・細胞株にて新規発生した遺伝子変化についても、異なる環境に腫瘍細胞が適応するための意味のある変化、すなわち腫瘍の進展・転移に関連する遺伝子異常など、精密医療の発展にとって有用な情報となる可能性がある。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (14 results)

All 2021 2020 2019 2018

All Journal Article (10 results) (of which Peer Reviewed: 8 results,  Open Access: 6 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Characterization of the large‐scale Japanese patient‐derived xenograft (J‐PDX) library2021

    • Author(s)
      Yagishita Shigehiro、Kato Ken、Takahashi Mami、Imai Toshio、Yatabe Yasushi、Kuwata Takeshi、Suzuki Mikiko、Ochiai Atsushi、Ohtsu Atsushi、Shimada Kazuaki、Nishida Toshirou、Hamada Akinobu、Mano Hiroyuki
    • Journal Title

      Cancer Science

      Volume: 112 Issue: 6 Pages: 2454-2466

    • DOI

      10.1111/cas.14899

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular and pathological analyses of gastric stump cancer by next-generation sequencing and immunohistochemistry2021

    • Author(s)
      Watanabe Masahiro、Kuwata Takeshi、Setsuda Ayumi、Tokunaga Masanori、Kaito Akio、Sugita Shizuki、Tonouchi Akiko、Kinoshita Takahiro、Nagino Masato
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 4165-4165

    • DOI

      10.1038/s41598-021-83711-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Real‐world data on microsatellite instability status in various unresectable or metastatic solid tumors2021

    • Author(s)
      Akagi Kiwamu、Oki Eiji、Taniguchi Hiroya、Nakatani Kaname、Aoki Daisuke、Kuwata Takeshi、Yoshino Takayuki
    • Journal Title

      Cancer Science

      Volume: 112 Issue: 3 Pages: 1105-1113

    • DOI

      10.1111/cas.14798

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical significance of lymphatic invasion in the esophageal region in patients with adenocarcinoma of the esophagogastric junction2020

    • Author(s)
      Sugita Shizuki、Kuwata Takeshi、Tokunaga Masanori、Kaito Akio、Watanabe Masahiro、Tonouchi Akiko、Kinoshita Takahiro、Nagino Masato
    • Journal Title

      Journal of Surgical Oncology

      Volume: 122 Issue: 3 Pages: 433-441

    • DOI

      10.1002/jso.25964

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Report of the use of patient‐derived xenograft models in the development of anticancer drugs in Japan2020

    • Author(s)
      Tsumura Ryo、Koga Yoshikatsu、Hamada Akinobu、Kuwata Takeshi、Sasaki Hiroki、Doi Toshihiko、Aikawa Katsuji、Ohashi Akihiro、Katano Ikumi、Ikarashi Yoshinori、Ito Mamoru、Ochiai Atsushi
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 9 Pages: 3386-3394

    • DOI

      10.1111/cas.14564

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of DNA integrity on the success rate of tissue‐based next‐generation sequencing: Lessons from nationwide cancer genome screening project SCRUM‐Japan GI‐SCREEN2020

    • Author(s)
      Kuwata Takeshi、Wakabayashi Masashi、Hatanaka Yutaka、Morii Eiichi、Oda Yoshinao、Taguchi Kenichi、Noguchi Masayuki、Ishikawa Yuichi、Nakajima Takashi、Sekine Shigeki、Nomura Shogo、Okamoto Wataru、Fujii Satoshi、Yoshino Takayuki、SCRUM‐Japan GI‐SCREEN Pathology Group
    • Journal Title

      Pathology International

      Volume: 70 Issue: 12 Pages: 932-942

    • DOI

      10.1111/pin.13029

    • NAID

      120007147854

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Impact of Molecular Subtype on Efficacy of Chemotherapy and Checkpoint Inhibition in Advanced Gastric Cancer2020

    • Author(s)
      Kubota Yohei、Kawazoe Akihito、Sasaki Akinori、Mishima Saori、Sawada Kentaro、Nakamura Yoshiaki、Kotani Daisuke、Kuboki Yasutoshi、Taniguchi Hiroya、Kojima Takashi、Doi Toshihiko、Yoshino Takayuki、Ishii Genichiro、Kuwata Takeshi、Shitara Kohei
    • Journal Title

      Clinical Cancer Research

      Volume: 26 Issue: 14 Pages: 3784-3790

    • DOI

      10.1158/1078-0432.ccr-20-0075

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] HER2 heterogeneity is a poor prognosticator for HER2-positive gastric cancer2019

    • Author(s)
      Kaito Akio、Kuwata Takeshi、Tokunaga Masanori、Shitara Kohei、Sato Reo、Akimoto Tetsuo、Kinoshita Takahiro
    • Journal Title

      World Journal of Clinical Cases

      Volume: 7 Issue: 15 Pages: 1964-1977

    • DOI

      10.12998/wjcc.v7.i15.1964

    • Related Report
      2019 Research-status Report
  • [Journal Article] Establishment of Novel Gastric Cancer Patient-Derived Xenografts and Cell Lines: Pathological Comparison between Primary Tumor, Patient-Derived, and Cell-Line Derived Xenografts2019

    • Author(s)
      Kuwata Takeshi、Yanagihara Kazuyoshi、Iino Yuki、Komatsu Teruo、Ochiai Atsushi、Sekine Shigeki、Taniguchi Hirokazu、Katai Hitoshi、Kinoshita Takahiro、Ohtsu Atsushi
    • Journal Title

      Cells

      Volume: 8 Issue: 6 Pages: 585-585

    • DOI

      10.3390/cells8060585

    • Related Report
      2019 Research-status Report
  • [Journal Article] Clinicopathological features of 22C3 PD-L1 expression with mismatch repair, Epstein?Barr virus status, and cancer genome alterations in metastatic gastric cancer2018

    • Author(s)
      Kawazoe Akihito、Shitara Kohei、Kuboki Yasutoshi、Bando Hideaki、Kojima Takashi、Yoshino Takayuki、Ohtsu Atsushi、Ochiai Atsushi、Togashi Yosuke、Nishikawa Hiroyoshi、Doi Toshihiko、Kuwata Takeshi
    • Journal Title

      Gastric Cancer

      Volume: 22 Issue: 1 Pages: 69-76

    • DOI

      10.1007/s10120-018-0843-9

    • NAID

      40021775208

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 精密医療の実現を目指した胃癌における分子プロファイルとその不均一性に関する検討2020

    • Author(s)
      桑田健
    • Organizer
      第66回日本病理学会秋季特別総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Clinicopathological factors associated with establishment of gastric cancer PDXs and cell lines2019

    • Author(s)
      Takeshi Kuwata
    • Organizer
      AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 胃癌治療のための新しい薬物開発プラットフォーム2019

    • Author(s)
      飯野由貴, 桑田健, 小松輝夫, 柳原五吉, 落合淳志
    • Organizer
      第78回日本癌学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 研究・新薬開発における病理学: 国立がん研究センター東病院における 胃癌PDX/細胞株樹立プロジェクト2018

    • Author(s)
      桑田 健
    • Organizer
      第22回日本がん分子標的治療学会学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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