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The genome analyses for advanced and recurrent ovarian clear cell carcinoma

Research Project

Project/Area Number 17H01587
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKyoto University

Principal Investigator

Ikuo Konishi  京都大学, 医学研究科, 名誉教授 (90192062)

Co-Investigator(Kenkyū-buntansha) 松村 謙臣  近畿大学, 医学部, 教授 (20452336)
村上 隆介  滋賀県立総合病院(研究所), その他部局等, 医長 (40782363)
山口 建  京都大学, 医学研究科, 講師 (20378772)
森 誠一  公益財団法人がん研究会, がんプレシジョン医療研究センター 次世代がん研究シーズ育成プロジェクト, プロジェクトリーダー (10334814)
日笠 幸一郎  関西医科大学, 医学部, 教授 (10419583)
山田 亮  京都大学, 医学研究科, 教授 (50301106)
安彦 郁  独立行政法人国立病院機構(京都医療センター臨床研究センター), 内分泌代謝高血圧研究部, 研究員 (20508246)
Brown John  京都大学, 医学研究科, 講師 (90583188)
榎本 隆之  新潟大学, 医歯学系, 教授 (90283754)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥42,380,000 (Direct Cost: ¥32,600,000、Indirect Cost: ¥9,780,000)
Fiscal Year 2019: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
Fiscal Year 2018: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2017: ¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000)
Keywords卵巣明細胞癌 / トランスレーショナルリサーチ / ゲノム解析 / トランスレーショナルリサ―チ / 卵巣癌
Outline of Final Research Achievements

The goal of genome analyses of ovarian clear cell carcinoma (OCCC) is to discover target genes related to resistance in cancer treatments. Firstly, genome analyses revealed that the copy number amplification at chromosome 17q21-24 is highly associated with recurrence OCCC cases. In vitro experiments using 13 OCCC cell lines, the level of amplification of PDK2 in the loci of chr17q21-24, an isozyme gene of pyruvate dehydrogenase kinase, significantly correlated with resistance to cisplatin through mitochondrial metabolism. Secondarily, from gene expression analyses between early and advanced stage OCCC groups using RNA sequencing, epithelial mesenchymal transition (EMT) genes are highly expressed in advanced stages. We discovered that SNAIL, one of EMT genes, induces myeloid derived immune suppressor cells (MDSC). Japanese Gynecologic Oncology Group collected almost 190 cases of OCCC surgical tumor tissues, which were applied to RNA sequencing for future datasets.

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義は、卵巣明細胞癌(OCCC)の腫瘍組織のゲノム解析から治療抵抗性に関わる因子を探求し基礎研究から再発症例におけるシスプラチン抵抗性とミトコンドリアにおける代謝や、進行症例における浸潤転移能と骨髄由来抑制細胞の増加を明らかにしたことである。さらに本研究の社会的意義は我が国の婦人科悪性腫瘍研究機構で全国規模のOCCCのRNAシークエンスのデータセット構築の先駆けとなったことである。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (19 results)

All 2020 2019 2018 2017

All Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Open Access: 7 results) Presentation (8 results) (of which Int'l Joint Research: 1 results) Book (1 results)

  • [Journal Article] Anti-VEGF therapy resistance in ovarian cancer is caused by GM-CSF-induced myeloid-derived suppressor cell recruitment.2020

    • Author(s)
      Horikawa N, Abiko K, Matsumura N, Baba T, Hamanishi J, Yamaguchi K, Murakami R, Taki M, Ukita M, Hosoe Y, Koshiyama M, Konishi I, Mandai M.
    • Journal Title

      Br J Cancer.

      Volume: 122(1) Issue: 6 Pages: 778-788

    • DOI

      10.1038/s41416-019-0725-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Homologous recombination deficiency status-based classification of high-grade serous ovarian carcinoma2020

    • Author(s)
      Takaya Hisamitsu、Nakai Hidekatsu、Takamatsu Shiro、Mandai Masaki、Matsumura Noriomi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 2757-2757

    • DOI

      10.1038/s41598-020-59671-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinically relevant molecular subtypes and genomic alteration-independent differentiation in gynecologic carcinosarcoma.2019

    • Author(s)
      Gotoh O, Sugiyama Y, Takazawa Y, Kato K, Tanaka N, Omatsu K, Takeshima N, Nomura H, Hasegawa K, Fujiwara K, Taki M, Matsumura N, Noda T, Mori S.
    • Journal Title

      Nat Commun.

      Volume: 10 Issue: 1 Pages: 4965-4965

    • DOI

      10.1038/s41467-019-12985-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acquisition of a side population fraction augments malignant phenotype in ovarian cancer.2019

    • Author(s)
      Yamanoi K, Baba T, Abiko K, Hamanishi J, Yamaguchi K, Murakami R, Taki M, Hosoe Y, Murphy SK, Konishi I, Mandai M, Matsumura N.
    • Journal Title

      Sci Rep.

      Volume: 9(1) Issue: 1 Pages: 14215-14215

    • DOI

      10.1038/s41598-019-50794-w

    • NAID

      120006822513

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The efficacy of secondary cytoreductive surgery for recurrent ovarian, tubal, or peritoneal cancer in Tian-model low-risk patients.2019

    • Author(s)
      So M, Miyamoto T, Murakami R, Abiko K, Hamanishi J, Baba T, Mandai M.
    • Journal Title

      J Gynecol Oncol.

      Volume: Nov;30(6) Issue: 6

    • DOI

      10.3802/jgo.2019.30.e100

    • NAID

      120006894002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The mesenchymal transition subtype more responsive to dose dense taxane chemotherapy combined with carboplatin than to conventional taxane and carboplatin chemotherapy in high grade serous ovarian carcinoma: A survey of Japanese Gynecologic Oncology Group study (JGOG3016A1).2019

    • Author(s)
      Ryusuke Murakami
    • Journal Title

      Gynecologic Oncology

      Volume: May;153(2) Issue: 2 Pages: 312-319

    • DOI

      10.1016/j.ygyno.2019.02.010

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] VISTA expressed in tumour cells regulates T cell function2018

    • Author(s)
      Mulati Kumuluzi、Hamanishi Junzo、Matsumura Noriomi、Chamoto Kenji、Mise Nathan、Abiko Kaoru、Baba Tsukasa、Yamaguchi Ken、Horikawa Naoki、Murakami Ryusuke、Taki Mana、Budiman Kharma、Zeng Xiang、Hosoe Yuko、Azuma Miyuki、Konishi Ikuo、Mandai Masaki
    • Journal Title

      British Journal of Cancer

      Volume: 120 Issue: 1 Pages: 115-127

    • DOI

      10.1038/s41416-018-0313-5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Adaptive mining and model building of medicinal chemistry data with a multi-metric perspective.2018

    • Author(s)
      Brown JB
    • Journal Title

      Future Med Chem.

      Volume: 10 Issue: 16 Pages: 1885-1887

    • DOI

      10.4155/fmc-2018-0188

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Snail promotes ovarian cancer progression by recruiting myeloid-derived suppressor cells via CXCR2 ligand upregulation.2018

    • Author(s)
      Taki M, Abiko K, Baba T, Hamanishi J, Yamaguchi K, Murakami R, Yamanoi K, Horikawa N, Hosoe Y, Nakamura E, Sugiyama A, Mandai M, Konishi I, Matsumura N.
    • Journal Title

      Nature communications

      Volume: Apr 27;9(1) Issue: 1 Pages: 1685-1685

    • DOI

      10.1038/s41467-018-03966-7

    • NAID

      120006462510

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Exome Sequencing Landscape Analysis in Ovarian Clear Cell Carcinoma Shed Light on Key Chromosomal Regions and Mutation Gene Networks.2017

    • Author(s)
      Murakami R, Matsumura N, Brown JB, Higasa K, Tsutsumi T, Kamada M, Abou-Taleb H, Hosoe Y, Kitamura S, Yamaguchi K, Abiko K, Hamanishi J, Baba T, Koshiyama M, Okuno Y, Yamada R, Matsuda F, Konishi I, Mandai M.
    • Journal Title

      The American Journal of Pathology

      Volume: 187 Issue: 10 Pages: 2246-2258

    • DOI

      10.1016/j.ajpath.2017.06.012

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 卵巣明細胞癌における包括的ゲノム・エピゲノム・代謝解析‐ 発癌過程のゲノム・エピゲノム異常が集約する糖代謝異常を標的とした新規治療の可能性 ‐2019

    • Author(s)
      山口 建
    • Organizer
      第71回日本産科婦人科学会学術講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] CD276 expression on ovarian cancer induces infiltration of myeloid derived suppressor cells2019

    • Author(s)
      Taito Miyamoto, Ryusuke Murakami, Sachiko Kitamura, Naoki Horikawa, Kaoru Abiko, Ken Yamaguchi, Junzo Hamanishi, Tsukasa Baba and Masaki Mandai
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Ferroptosis resistance may be associated with epithelial-mesenchymal transition2019

    • Author(s)
      Yoko Furutake, Ken Yamaguchi, Sachiko Kitamura, Shiro Takamatsu, Naoki Horikawa, Junzo Hamanishi, Masaki Mandai
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Bevacizumab maintenance therapy for the histopathological mesenchymal transition type of high-grade serous ovarian carcinoma could well extend the overall survival2019

    • Author(s)
      Kentaro Ishida , Ryusuke Murakami, Akihiko Ueda ,Sachiko Kitamura, Naoki Horikawa, Yoshitsugu Chigusa, Kaoru Abiko, Ken Yamaguchi, Junzo Hamanishi, Masaki Mandai
    • Organizer
      The 7th Biennial Meeting of Asian Society of Gynecologic Oncology
    • Related Report
      2019 Annual Research Report
  • [Presentation] The laparoscopic findings of the mesenchymal transition type of high grade serous ovarian carcinoma is characterized by military intraperitoneal dissemination2019

    • Author(s)
      Ryusuke Murakami Kentaro Ishida, Shunsuke Kawahara, Taito Miyamoto, Miyuki Ito, Kaoru Abiko, Akihito Horie, Junzo Hamanishi, Eiji Kondoh, Tsukasa Baba, Masaki Mandai
    • Organizer
      The 17th Biennial Meeting of the International Gynecologic Cancer Society (IGCS 2018) 14-16 Sep 2018. Kyoto
    • Related Report
      2018 Annual Research Report
  • [Presentation] Genomic alterations induces metabolic change through the activation of PDK2 in ovarian clear cell carcinoma.2018

    • Author(s)
      Sachiko Kitamura, Ken Yamaguchi, Ryusuke Murakami, Kaoru Abiko Junzo Hamanishi, Tsukasa Baba, Noriomi Matsumura, Masaki Mandai
    • Organizer
      第70回日本産科婦人科学会学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Is the mesenchymal transition subtype more responsive to dose dense taxane chemotherapy combined with carboplatin (ddTC) than to conventional taxane and carboplatin chemotherapy (TC) in high grade serous ovarian carcinoma? A survey of Japanese Gynecology Oncology Group study (JGOG3016A1)2017

    • Author(s)
      Ryusuke Murakami, Noriomi Matsumura, Hiroshi Tanabe, Hirofumi Michimae, Mayu Yunokawa, Haruko Iwase, Motoi Sasagawa, Toshiaki Nakamura, Osamu Tokuyama, Masashi Takano, Toru Sugiyama, Takashi Sawasaki, Seiji Isonishi, Kazuhiro Takehara, Hidekatsu Nakai, Aikou Okamoto, Masaki Mandai, Ikuo Konishi
    • Organizer
      ASCO2017, symposium, J Clin Oncol 35, 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PDK2 contributes to the platinum resistance of ovarian clear cell carcinoma accompanied by chromosome 17q amplification2017

    • Author(s)
      Sachiko Kitamura, Ken Yamaguchi, Ryusuke Murakami, Kaoru Abiko Junzo Hamanishi, Tsukasa Baba, Noriomi Matsumura, Masaki Mandai
    • Organizer
      日本癌学会
    • Related Report
      2017 Annual Research Report
  • [Book] Precision Medicine in Gynecology and Obstetrics.2017

    • Author(s)
      Ikuo Konishi
    • Total Pages
      250
    • Publisher
      Springer
    • ISBN
      9789811024894
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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