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Whole transcriptome analysis and novel therapeutic targets in biliary tract cancer

Research Project

Project/Area Number 26461040
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionNational Cancer Center Japan

Principal Investigator

Arai Yasuhito  国立研究開発法人国立がん研究センター, 研究所, 主任研究員 (80222727)

Co-Investigator(Renkei-kenkyūsha) SHIBATA Tatsuhiro  国立研究開発法人国立がん研究センター研究所, がんゲノミクス研究分野, 分野長 (90311414)
TOTOKI Yasushi  国立研究開発法人国立がん研究センター研究所, がんゲノミクス研究分野, ユニット長 (10373333)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords胆道がん / トランスクリプトーム / 融合遺伝子 / 分子診断 / 治療標的遺伝子 / 分子標的
Outline of Final Research Achievements

Biliary tract cancer (BTC) is an intractable cancer, with limited therapeutic options. To find out cancer driver alterations and biomarkers for personalized therapy, we performed whole transcriptome sequencing analyses of 160 BTC cases. FGFR2 fusion kinase genes we identified are one of the high-potential therapeutic targets of BTC. Novel fusion genes, ATP1B-PRKACA/PRKACB involving cAMP-dependent protein kinase (PKA) signal components (PRKACA and PRKACB) were identified in extrahepatic cholangiocarcinoma. The fusions robustly induced expression of the PRKACA and PRKACB, and demonstrated increased or comparative PKA activity compared to wild-type PKA activating downstream MAPK. These analyses pave the way to genotype-based actionable target therapy.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (9 results)

All 2017 2016 2015 2014

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 2 results) Presentation (4 results) Book (1 results)

  • [Journal Article] NUTM2A-CIC fusion small round cell sarcoma: A genetically distinct variant of CIC-rearranged sarcoma2017

    • Author(s)
      Sugita S, Arai Y, Aoyama T, Asanuma H, Mukai W, Hama N, Emori M, Shibata T, Hasegawa T
    • Journal Title

      Human Pathology

      Volume: 印刷中 Pages: 225-230

    • DOI

      10.1016/j.humpath.2017.01.012

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] CIC Break-Apart Fluorescence In Situ Hybridization Misses a Subset of CIC-DUX4 Sarcomas: A Clinicopathological and Molecular Study2017

    • Author(s)
      Yoshida A, Arai Y, Kobayashi E, Yonemori K, Ogura K, Hama N, Mukai W, Motoi T, Kawai A, Shibata T, N Hiraoka
    • Journal Title

      Histopathology

      Volume: 印刷中 Issue: 3 Pages: 461-469

    • DOI

      10.1111/his.13252

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heat Shock Protein 90 Is a Potential Therapeutic Target in Cholangiocarcinoma.2015

    • Author(s)
      Shirota T, Ojima H, Hiraoka N, Shimada K, Rokutan H, Arai Y, Kanai Y, Miyagawa S, Shibata T.
    • Journal Title

      Mol Cancer Ther.

      Volume: 14 Issue: 9 Pages: 1985-93

    • DOI

      10.1038/ng.3375

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma.2014

    • Author(s)
      Arai Y, Totoki Y, Hosoda F, Shirota T, Hama N, Nakamura H, Ojima, Furuta K, Shimada K, Okusaka T, Kosuge T, Shibata T.
    • Journal Title

      Hepatology

      Volume: 59 Issue: 4 Pages: 1427-1434

    • DOI

      10.1002/hep.26890

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] E7090, a novel and selective FGFR inhibitor, for the treatment of cholangiocarcinoma cells harboring FGFR2-fusion genes2017

    • Author(s)
      Watanabe-Miyano S, Arai Y, Matsui Junji, Shibata T
    • Organizer
      AACR annual meeting 2017
    • Place of Presentation
      Washington Convention Center (Washington DC, USA)
    • Year and Date
      2017-04-01
    • Related Report
      2016 Annual Research Report
  • [Presentation] Oncogenic driver fusion genes in biliary tract cancer2016

    • Author(s)
      新井康仁、中村浩実、十時 泰、濱 奈津子、尾島英知、細田文恵、島田和明、森実千種、奥坂拓志、柴田龍弘
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜 (神奈川県横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] 網羅的シークエンス解析による胆管がん分子標的の同定2015

    • Author(s)
      新井康仁、中村浩実、十時 泰、代田智樹、濱 奈津子、尾島英知、細田文恵、島田和明、森実千種、奥坂拓志、柴田龍弘
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] 胆管がんにおける分子標的としてのFGFR2融合遺伝子の同定2014

    • Author(s)
      新井康仁、十時 泰、細田文恵、代田智樹、濱 奈津子、中村浩実、尾島英知、古田 耕、島田和明、小菅智男、森実千種、奥坂拓志、柴田龍弘
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Book] 医学の歩み-特集がんゲノム研究の進歩-固形がんにおける融合遺伝子の解析と治療への展開2014

    • Author(s)
      新井康仁
    • Total Pages
      134
    • Publisher
      医歯薬出版
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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