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Analysis of the oncogenesis mechanism and the pathology of malignant mesothelioma based on BAP1 gene mutation

Research Project

Project/Area Number 17K08731
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionHyogo Medical University

Principal Investigator

Tsujimura Tohru  兵庫医科大学, 医学部, 教授 (20227408)

Co-Investigator(Kenkyū-buntansha) 佐藤 鮎子  兵庫医科大学, 医学部, 講師 (20419823)
阿部 晋也  兵庫医科大学, 医学部, 助教 (70596725)
篠原 義康  兵庫医科大学, 医学部, 助教 (60723509)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords悪性中皮腫 / BAP1 / 細胞増殖 / 細胞遊走 / 予後 / 病理学
Outline of Final Research Achievements

Using the genome editing technique, p16-KO mesothelial cells, BAP1-KO mesothelial cells, and p16 & BAP1-DKO mesothelial cells were produced. In p16-KO mesothelial cells, no obvious change was observed in cell morphology, proliferative ability, and migratory ability, whereas in BAP1-KO mesothelial cells, the cells became larger and migratory ability, but not proliferative ability, was suppressed. By gene expression profile analysis, we found a cell migration factor X whose expression is markedly reduced in BAP1-KO mesothelial cells. BAP1 immunohistochemistry of epithelioid mesothelioma revealed that BAP1-positive cases had a poorer prognosis than BAP1-negative cases. BAP1 mutations are frequently found in epithelioid mesothelioma but appear to be less associated with malignancy.

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、BAP1変異は細胞増殖能よりも細胞遊走能に関与していることが明らかになり、それを担う候補分子として細胞遊走因子Xを見出している点に学術的意義がある。これらの知見は、BAP1変異を基軸とした悪性中皮腫の治療開発の重要性を支持するものであり、悪性中皮腫患者への福音になると期待される点に社会的意義がある。

Report

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

    (26 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: 3 results) Presentation (16 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results)

  • [Journal Article] Clinical feature of diagnostic challenging cases for pleural biopsy in patient with malignant pleural mesothelioma.2020

    • Author(s)
      Hashimoto M, Sato A, Kuroda A, Nakamura A, Nakamichi T, Kondo N, Yuki M, Nabeshima K, Tsujimura T, Hasegawa S.
    • Journal Title

      Gen Thorac Cardiovasc Surg.

      Volume: - Issue: 8 Pages: 820-827

    • DOI

      10.1007/s11748-020-01295-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The mTOR Signaling Pathway Is Associated With the Prognosis of Malignant Pleural Mesothelioma After Multimodality Therapy2019

    • Author(s)
      Kuroda A, Matsumoto S, Fukuda A, Nakamichi T, Nakamura A, Hashimoto M, Takuwa T, Kondo N, Tsujimura T, Nakano T, Hasegawa S
    • Journal Title

      Anticancer Research

      Volume: 39 Issue: 11 Pages: 6241-6247

    • DOI

      10.21873/anticanres.13833

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytoplasmic MTAP expression loss detected by immunohistochemistry correlates with 9p21 homozygous deletion detected by FISH in pleural effusion cytology of mesothelioma.2019

    • Author(s)
      Hamasaki M, Kinoshita Y, Yoshimura M, Matsumoto S, Kamei T, Hiroshima K, Sato A, Tsujimura T, Kawahara K, Nabeshima K.
    • Journal Title

      Histopathology

      Volume: 75 Issue: 1 Pages: 153-155

    • DOI

      10.1111/his.13872

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular pathways and diagnosis in malignant mesothelioma: A review of the 14th International Conference of the International Mesothelioma Interest Group2019

    • Author(s)
      Chapel David B.、Churg Andrew、Santoni-Rugiu Eric、Tsujimura Tohru、Hiroshima Kenzo、Husain Aliya N.
    • Journal Title

      Lung Cancer

      Volume: 127 Pages: 69-75

    • DOI

      10.1016/j.lungcan.2018.11.032

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Surgical Risk and Survival Associated With Less Invasive Surgery for Malignant Pleural Mesothelioma2019

    • Author(s)
      Hasegawa S, Kondo N, Matsumoto S, Takuwa T, Hashimoto M, Kuroda A, Nakamichi T, Kamikonya N, Tsujimura T, Nakano T
    • Journal Title

      Seminars in Thoracic and Cardiovascular Surgery

      Volume: 31 Issue: 2 Pages: 301-309

    • DOI

      10.1053/j.semtcvs.2019.01.010

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] A combination of MTAP and BAP1 immunohistochemistry is effective for distinguishing sarcomatoid mesothelioma from fibrous pleuritis2018

    • Author(s)
      Kinoshita Yoshiaki、Hamasaki Makoto、Yoshimura Masayo、Matsumoto Shinji、Sato Ayuko、Tsujimura Tohru、Ueda Hitoshi、Makihata Satoshi、Kato Fumiaki、Iwasaki Akinori、Nabeshima Kazuki
    • Journal Title

      Lung Cancer

      Volume: 125 Pages: 198-204

    • DOI

      10.1016/j.lungcan.2018.09.019

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pulmonary Regnase-1 orchestrates the interplay of epithelium and adaptive immune systems to protect against pneumonia2018

    • Author(s)
      Nakatsuka Yoshinari、Vandenbon Alexis、Mino Takashi、Yoshinaga Masanori、Uehata Takuya、Cui Xiaotong、Sato Ayuko、Tsujimura Tohru、Suzuki Yutaka、Sato Atsuyasu、Handa Tomohiro、Chin Kazuo、Sawa Teiji、Hirai Toyohiro、Takeuchi Osamu
    • Journal Title

      Mucosal Immunology

      Volume: AOP Issue: 4 Pages: 1203-1218

    • DOI

      10.1038/s41385-018-0024-5

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Integrative Molecular Characterization of Malignant Pleural Mesothelioma2018

    • Author(s)
      Hmeljak Julija、TCGA Research Network et al (他58名、48番目)
    • Journal Title

      Cancer Discovery

      Volume: 8 Issue: 12 Pages: 1548-1565

    • DOI

      10.1158/2159-8290.cd-18-0804

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Positive correlation between postoperative tumor recurrence and changes in circulating tumor cell counts in pulmonary venous blood (pvCTC) during surgical manipulation in non-small cell lung cancer2018

    • Author(s)
      Hashimoto Masaki、Tanaka Fumihiro、Yoneda Kazue、Takuwa Teruhisa、Matsumoto Seiji、Okumura Yoshitomo、Kondo Nobuyuki、Tsujimura Tohru、Nakano Takashi、Hasegawa Seiki
    • Journal Title

      Journal of Thoracic Disease

      Volume: 10 Issue: 1 Pages: 298-306

    • DOI

      10.21037/jtd.2017.12.56

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma2017

    • Author(s)
      Kinoshita Yoshiaki、Hida Tomoyuki、Hamasaki Makoto、Matsumoto Shinji、Sato Ayuko、Tsujimura Tohru、Kawahara Kunimitsu、Hiroshima Kenzo、Oda Yoshinao、Nabeshima Kazuki
    • Journal Title

      Cancer Cytopathology

      Volume: 126 Issue: 1 Pages: 54-63

    • DOI

      10.1002/cncy.21928

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 悪性胸膜中皮腫診断における胸水セルブロック法の有用性についての単一施設後ろ向き研究2019

    • Author(s)
      橋本 昌樹, 中道 徹, 中村 晃史, 黒田 鮎美, 松本 成司, 近藤 展行, 結城 美智子, 佐藤 鮎子, 辻村 亨, 長谷川 誠紀
    • Organizer
      第60回日本肺癌学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 呼吸器(ヨーロッパ細胞学会の内容から) 中皮腫の細胞診診断update 中皮腫の遺伝子変異に基づく補助診断法(シンポジウム)2019

    • Author(s)
      濱崎 慎, 木下 義晃, 松本 慎二, 佐藤 鮎子, 辻村 亨, 河原 邦光, 廣島 健三, 亀井 敏昭, 鍋島 一樹
    • Organizer
      第58回日本臨床細胞学会秋期大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 中皮腫アップデート 早期診断を目指して2019

    • Author(s)
      辻村 亨, 結城 美智子, 篠原 義康, 隅田 安由美, 佐藤 鮎子
    • Organizer
      第58回日本臨床細胞学会秋期大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 胸水セルブロックによる悪性胸膜中皮腫確定診断の可能性確認試験2019

    • Author(s)
      橋本 昌樹, 南 俊行, 佐藤 鮎子, 中道 徹, 中村 晃史, 黒田 鮎美, 松本 成司, 近藤 展行, 横井 崇, 結城 美智子, 木島 貴志, 鍋島 一樹, 辻村 亨, 長谷川 誠紀
    • Organizer
      第1回日本石綿・中皮腫学会(JAMIG)学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 悪性胸膜中皮腫の早期発見 胸水セルブロックを用いた免疫染色の有用性2019

    • Author(s)
      小畑 有未, 結城 美智子, 佐藤 鮎子, 篠原 義康, 辻村 亨
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 悪性胸膜中皮腫におけるTRAF7遺伝子変異の解析2019

    • Author(s)
      佐藤 鮎子, 結城 美智子, 篠原 義康, 竹下 純平, 油谷 浩幸, 辻村 亨
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 悪性中皮腫細胞株におけるp62/SQSTM1の機能解析2019

    • Author(s)
      篠原 義康, 佐藤 鮎子, 結城 美智子, 辻村 亨
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Malignant pleural mesothelioma with TRAF7 gene mutation2019

    • Author(s)
      Tsujimura T, Sato A, Yuki M, Shinohara Y, Takeshita J, Aburatani H, Sekido Y
    • Organizer
      the 31st European Congress of Pathology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The role of EZH2 in the proliferation, migration, and tumorigenicity of malignant mesothelioma.2018

    • Author(s)
      Tsujimura T, Sato A, Yuki M, Abe S, Shinohara Y
    • Organizer
      14th International Conference of the International Mesothelioma Interest Group
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Immunohistochemical detection of MTAP or BAP1 protein loss in tissues and cell blocks for diagnosis of mesothelioma2018

    • Author(s)
      Nabeshima K, Kinoshita Y, Hamasaki M, Hida T, Matsumoto S, Sato A, Tsujimura T, Kawahara K, Hiroshima K, Iwasaki A, Oda Y
    • Organizer
      14th International Conference of the International Mesothelioma Interest Group
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 中皮腫細胞診のupdate2018

    • Author(s)
      辻村 亨, 佐藤 鮎子, 結城 美智子, 隅田 安由美, 阿部 晋也, 篠原 義康
    • Organizer
      第59回日本臨床細胞学会総会春期大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 悪性中皮腫におけるEZH2の生物学的作用についての解析2018

    • Author(s)
      篠原 義康, 佐藤 鮎子, 阿部 晋也, 結城 美智子, 辻村 亨
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 中皮腫の細胞像、組織像そして最近の話題2018

    • Author(s)
      鍋島 一樹,濱崎 慎,木下 義晃,松本 慎二,吉村 雅代,樋田 知之,佐藤 鮎子,辻村 亨,河原 邦光,廣島 健三,亀井 敏昭,小田 義直
    • Organizer
      第57回日本臨床細胞学会秋期大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 肉腫型悪性胸膜中皮腫と線維性胸膜炎の鑑別におけるMTAP IHC及びBAP1 IHCの有用性2018

    • Author(s)
      木下 義晃, 濱崎 慎, 吉村 雅代, 松本 慎二, 佐藤 鮎子, 辻村 亨, 鍋島 一樹
    • Organizer
      第59回日本肺癌学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 悪性胸膜中皮腫の胸水細胞診におけるBAP1免疫染色の有用性2017

    • Author(s)
      辻村 亨, 佐藤 鮎子, 隅田 安由美, 篠原 義康, 阿部 晋也
    • Organizer
      第58回日本臨床細胞学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 中皮腫の細胞診update2017

    • Author(s)
      鍋島 一樹, 木下 義晃, 松本 慎二, 樋田 知之, 佐藤 鮎子, 辻村 亨, 河原 邦光, 廣島 健三, 亀井 敏昭, 小田 義直
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Research-status Report

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

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