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Identification of pathogenesis of ovarian clear cell carcinoma by topographic single cell sequencing

Research Project

Project/Area Number 20K21647
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research InstitutionNiigata University

Principal Investigator

Enomoto Takayuki  新潟大学, 医歯学系, 教授 (90283754)

Co-Investigator(Kenkyū-buntansha) 井ノ上 逸朗  国立遺伝学研究所, ゲノム・進化研究系, 教授 (00192500)
吉原 弘祐  新潟大学, 医歯学系, 研究准教授 (40547535)
安達 聡介  新潟大学, 医歯学総合病院, 助教 (50613147)
田村 亮  新潟大学, 医歯学総合病院, 助教 (70650620)
石黒 竜也  新潟大学, 医歯学総合病院, 助教 (80625690)
Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2020: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords卵巣癌 / 明細胞癌 / 子宮内膜症 / 子宮内膜 / ゲノム / 単一腺管シークエンス / 正常子宮内膜 / シングルセルシークエンス / 癌遺伝子
Outline of Research at the Start

我々は卵巣明細胞癌の発生起源である子宮内膜症に対するゲノム解析を行い、子宮内膜症にすでに癌遺伝子変異が存在することを報告している。卵巣明細胞癌の発症には、上記遺伝子変異以外にもゲノム・エピゲノム異常が複雑に関与している。そこで本研究では、卵巣明細胞癌症例の子宮内膜症から卵巣明細胞癌に移行する部位に注目し、同部位から単一細胞をレーザーマイクロダイセクションで一つずつ切り出し、微量DNAを用いたシークエンス解析を行う。位置情報を反映した単一細胞シークエンス解析により、子宮内膜症から卵巣明細胞癌に移行するにつれて蓄積されるゲノム・エピゲノム異常を明らかにし、卵巣明細胞癌の発症メカニズムを解明する。

Outline of Final Research Achievements

We aimed to identify genomic and epigenomic alterations from endometriosis to ovarian cancers. Single-cell sequencing analysis will reveal the genomic and epigenomic abnormalities that accumulate during the transition from endometriosis to ovarian clear cell carcinoma and elucidate the pathogenic mechanism of ovarian clear cell carcinoma. To this end, we sampled normal endometrium, endometriosis, and ovarian clear cell carcinoma, and performed whole-exome sequencing for normal endometrium, endometriosis, atypical endometriosis, and carcinoma. In addition, we isolated single glands from normal endometrium tissue by laser microdissection, and conducted whole genome sequencing for them. We confirmed that we could extract DNA from cells after laser microdissection and perform whole genome sequencing.

Academic Significance and Societal Importance of the Research Achievements

卵巣明細胞がんは日本で頻度の高い卵巣がんであり、プラチナ併用化学療法に抵抗性を示すことから、発症予防が重要になる。正常子宮内膜から子宮内膜症、明細胞癌に移行するにつれて蓄積されるゲノム異常を同定することができ、今後子宮内膜症や卵巣明細胞癌の発症予防に役立つ情報を得ることができた。

Report

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

    (11 results)

All 2022 2021 2020

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 8 results)

  • [Journal Article] Spatiotemporal dynamics of clonal selection and diversification in normal endometrial epithelium2022

    • Author(s)
      Yamaguchi Manako、Nakaoka Hirofumi、Suda Kazuaki、Yoshihara Kosuke、Ishiguro Tatsuya、Yachida Nozomi、Saito Kyota、Ueda Haruka、Sugino Kentaro、Mori Yutaro、Yamawaki Kaoru、Tamura Ryo、Revathidevi Sundaramoorthy、Motoyama Teiichi、Tainaka Kazuki、Verhaak Roel G. W.、Inoue Ituro、Enomoto Takayuki
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 943-943

    • DOI

      10.1038/s41467-022-28568-2

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] APOBEC mediated mutagenesis drives genomic heterogeneity in endometriosis2022

    • Author(s)
      Revathidevi Sundaramoorthy、Nakaoka Hirofumi、Suda Kazuaki、Fujito Naoko、Munirajan Arasambattu Kannan、Yoshihara Kosuke、Enomoto Takayuki、Inoue Ituro
    • Journal Title

      Journal of Human Genetics

      Volume: 67 Issue: 6 Pages: 323-329

    • DOI

      10.1038/s10038-021-01003-y

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proposing a molecular classification associated with hypercoagulation in ovarian clear cell carcinoma2021

    • Author(s)
      Tamura Ryo、Yoshihara Kosuke、Matsuo Koji、Yachida Nozomi、Miyoshi Ai、Takahashi Kotaro、Sugino Kentaro、Yamaguchi Manako、Mori Yutaro、Suda Kazuaki、Ishiguro Tatsuya、Okuda Shujiro、Motoyama Teiichi、Nakaoka Hirofumi、Kikuchi Akira、Ueda Yutaka、Inoue Ituro、Enomoto Takayuki
    • Journal Title

      Gynecologic Oncology

      Volume: 163 Issue: 2 Pages: 327-333

    • DOI

      10.1016/j.ygyno.2021.08.009

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The New Era of Three-Dimensional Histoarchitecture of the Human Endometrium2021

    • Author(s)
      Yamaguchi Manako、Yoshihara Kosuke、Yachida Nozomi、Suda Kazuaki、Tamura Ryo、Ishiguro Tatsuya、Enomoto Takayuki
    • Journal Title

      Journal of Personalized Medicine

      Volume: 11 Issue: 8 Pages: 713-713

    • DOI

      10.3390/jpm11080713

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Clinical Significance of Mesenteric Lymph Node Involvement in the Pattern of Liver Metastasis in Patients with Ovarian Cancer2021

    • Author(s)
      Tanaka Kana、Shimada Yoshifumi、Nishino Koji、Yoshihara Kosuke、Nakano Masato、Kameyama Hitoshi、Enomoto Takayuki、Wakai Toshifumi
    • Journal Title

      Annals of Surgical Oncology

      Volume: 28 Issue: 12 Pages: 7606-7613

    • DOI

      10.1245/s10434-021-09899-8

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] How Does Endometriosis Lead to Ovarian Cancer? The Molecular Mechanism of Endometriosis-Associated Ovarian Cancer Development2021

    • Author(s)
      Yachida Nozomi、Yoshihara Kosuke、Yamaguchi Manako、Suda Kazuaki、Tamura Ryo、Enomoto Takayuki
    • Journal Title

      Cancers

      Volume: 13 Issue: 6 Pages: 1439-1439

    • DOI

      10.3390/cancers13061439

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Three-dimensional understanding of the morphological complexity of the human uterine endometrium2021

    • Author(s)
      Yamaguchi Manako、Yoshihara Kosuke、Suda Kazuaki、Nakaoka Hirofumi、Yachida Nozomi、Ueda Haruka、Sugino Kentaro、Mori Yutaro、Yamawaki Kaoru、Tamura Ryo、Ishiguro Tatsuya、Motoyama Teiichi、Watanabe Yu、Okuda Shujiro、Tainaka Kazuki、Enomoto Takayuki
    • Journal Title

      iScience

      Volume: 24 Issue: 4 Pages: 102258-102258

    • DOI

      10.1016/j.isci.2021.102258

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biological significance of KRAS mutant allele expression in ovarian endometriosis2021

    • Author(s)
      Yachida Nozomi、Yoshihara Kosuke、Suda Kazuaki、Nakaoka Hirofumi、Ueda Haruka、Sugino Kentaro、Yamaguchi Manako、Mori Yutaro、Yamawaki Kaoru、Tamura Ryo、Ishiguro Tatsuya、Kase Hiroaki、Motoyama Teiichi、Enomoto Takayuki
    • Journal Title

      Cancer Science

      Volume: 112 Issue: 5 Pages: 2020-2032

    • DOI

      10.1111/cas.14871

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of in vitro 3D spheroid cell cultivation from human gynecologic cancer tissues2021

    • Author(s)
      Ueda Haruka、Mori Yutaro、Yamawaki Kaoru、Ishiguro Tatsuya、Ohata Hirokazu、Sato Ai、Sugino Kentaro、Yachida Nozomi、Yamaguchi Manako、Suda Kazuaki、Tamura Ryo、Yoshihara Kosuke、Okamoto Koji、Enomoto Takayuki
    • Journal Title

      STAR Protocols

      Volume: 2 Issue: 1 Pages: 100354-100354

    • DOI

      10.1016/j.xpro.2021.100354

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clonal lineage from normal endometrium to ovarian clear cell carcinoma through ovarian endometriosis2020

    • Author(s)
      Suda Kazuaki、Cruz Diaz Luis Antonio、Yoshihara Kosuke、Nakaoka Hirofumi、Yachida Nozomi、Motoyama Teiichi、Inoue Ituro、Enomoto Takayuki
    • Journal Title

      Cancer Science

      Volume: - Issue: 8 Pages: 3000-3009

    • DOI

      10.1111/cas.14507

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ARID1A protein expression is retained in ovarian endometriosis with ARID1A loss-of-function mutations: implication for the two-hit hypothesis2020

    • Author(s)
      Yachida Nozomi、Yoshihara Kosuke、Suda Kazuaki、Nakaoka Hirofumi、Ueda Haruka、Sugino Kentaro、Yamaguchi Manako、Mori Yutaro、Yamawaki Kaoru、Tamura Ryo、Ishiguro Tatsuya、Isobe Masanori、Motoyama Teiichi、Inoue Ituro、Enomoto Takayuki
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 14260-14260

    • DOI

      10.1038/s41598-020-71273-7

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access

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Published: 2020-08-03   Modified: 2023-01-30  

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