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Molecular pathology of EGFR-mutated lung adenocarcinoma

Research Project

Project/Area Number 18K15086
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49020:Human pathology-related
Research InstitutionYokohama City University

Principal Investigator

MATSUMURA Mai  横浜市立大学, 医学部, 助教 (50812997)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsEGFR変異肺腺癌 / MUC21 / 微小乳頭状亜型 / 全エクソーム解析 / バイオインフォマティクス解析 / 肺癌 / 肺腺癌 / EGFR変異
Outline of Final Research Achievements

Our recent study demonstrated that malignant grade of EGFR-mutated lung adenocarcinoma (LADC) was determined by micropapillary (mPAP) element. I revealed that MUC21 was related to mPAP element of EGFR-mutated LADCs, and the tumors expressed MUC21 protein had poor prognosis. To uncover the potential molecular basis of mPAP element, I investigated somatic mutations specific to mPAP element in EGFR-mutated LADC. mPAP and other elements were separately collected from frozen tissue sections of EGFR-mutated LADC by the laser capture microdissection system and were subjected to whole exomes sequencing analyses. Through bioinformatics analysis, somatic mutations which was cofirmed by sanger-sequencing specific to mPAP elements were identified. Finally, I made “Highly malignant EGFR-mutated LADCs gene panel”. These gene mutations might be related to the highly malignant activity of mPAP element.

Academic Significance and Societal Importance of the Research Achievements

これまで肺がん臨床の現場で分子治療標的となる遺伝子変異は、腫瘍発生に関わるドライバー変異であった。我々が作成した「高悪性度EGFR肺腺癌パネル」に含まれる後発変異が治療標的となれば、EGFRチロシンキナーゼ阻害薬(EGFR-TKI)との併用により、腫瘍の悪性化や薬剤耐性化の阻止に役立つ可能性がある。

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

    (23 results)

All 2021 2020 2019 2018

All Journal Article (14 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 14 results,  Open Access: 7 results) Presentation (9 results)

  • [Journal Article] The nonsmokers’ and smokers’ pathways in lung adenocarcinoma: Histological progression and molecular bases2021

    • Author(s)
      Okudela Koji、Matsumura Mai、Arai Hiromasa、Woo Tetsukan
    • Journal Title

      Cancer Science

      Volume: 112 Issue: 9 Pages: 3411-3418

    • DOI

      10.1111/cas.15031

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Frequent DYRK2 gene amplification in micropapillary element of lung adenocarcinoma - an implication in progression in EGFR-mutated lung adenocarcinoma.2021

    • Author(s)
      Koike C, Okudela K, Matsumura M, Mitsui H, Suzuki T, Arai H, Kataoka T, Ishikawa Y, Umeda S, Tateishi Y, Ohashi
    • Journal Title

      Histology and Histopathology

      Volume: 36(3) Pages: 305-315

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A lung tumor with features of salivary duct carcinoma2021

    • Author(s)
      Sato Keisuke、Matsumura Mai、Anzai Yoko、Arai Hiromasa、Sekiya Motoki、Sugiyama Misaki、Kataoka Toshiaki、Koike Chihiro、Ohashi Kenichi、Okudela Koji
    • Journal Title

      Pathology International

      Volume: 71 Issue: 4 Pages: 284-286

    • DOI

      10.1111/pin.13072

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Frequent DYRK2 gene amplification in micropapillary element of lung adenocarcinoma - an implication in progression in EGFR-mutated lung adenocarcinoma2020

    • Author(s)
      Chihiro Koike, Koji Okudela, Mai Matsumura, Hideaki Mitsui, Takehisa Suzuki, Hiromasa Arai, Toshiaki Kataoka, Yoshihiro Ishikawa, Shigeaki Umeda, Yoko Tateishi, Kenichi Ohashi
    • Journal Title

      Histology and Histopathology .

      Volume: Online ahead of print.

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Unilateral upper lung-field pulmonary fibrosis radiologically consistent with pleuroparenchymal fibroelastosis after thoracic surgery: Clinical and radiological courses with autopsy findings2020

    • Author(s)
      Sekine Akimasa、Satoh Hiroaki、Takemura Tamiko、Matsumura Mai、Okudela Koji、Iwasawa Tae、Okabayashi Hiroko、Ikeda Satoshi、Yamakawa Hideaki、Oda Tsuneyuki、Okuda Ryo、Kitamura Hideya、Baba Tomohisa、Komatsu Shigeru、Hagiwara Eri、Ogura Takashi
    • Journal Title

      Respiratory Investigation

      Volume: 58 Issue: 6 Pages: 448-456

    • DOI

      10.1016/j.resinv.2020.05.001

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] An NRAS mutation in primary malignant melanoma of the lung: a case report2020

    • Author(s)
      Hibiya Takashi、Tanaka Meiro、Matsumura Mai、Aoki Ayako、Ikegami Tadashi、Okudela Koji、Kawano Naomi、Ohashi Kenichi
    • Journal Title

      Diagnostic Pathology

      Volume: 15 Issue: 1

    • DOI

      10.1186/s13000-020-0928-8

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Miliary Lung Metastases from Genital Large Cell Neuroendocrine Carcinomas2019

    • Author(s)
      Sekine Akimasa、Satoh Makiko、Okudela Koji、Matsumura Mai、Morishita Yukio、Minami Yuko、Hayashihara Kenji、Saito Takefumi、Iwasawa Tae、Ogura Takashi
    • Journal Title

      Internal Medicine

      Volume: 58 Issue: 8 Pages: 1127-1130

    • DOI

      10.2169/internalmedicine.1220-18

    • NAID

      130007632761

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2019-04-15
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Specific expression of MUC21 in micropapillary elements of lung adenocarcinomas -Implications for the progression of EGFR-mutated lung adenocarcinomas,2019

    • Author(s)
      Matsumura M, Okudela K, Nakashima Y, Mitsui H, Denda-Nagai K, Suzuki T, Arai H, Umeda S, Tateishi Y, Koike C, Kataoka T, Irimura T, Ohashi.
    • Journal Title

      PLoS One

      Volume: 14 Issue: 4 Pages: e0215237-e0215237

    • DOI

      10.1371/journal.pone.0215237

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Unique expression profiles of mucin proteins in interstitial pneumonia-associated lung adenocarcinomas.2019

    • Author(s)
      Kataoka T1, Okudela K2, Nakashima Y1, Mitsui H1, Matsumura M1, Umeda S1, Arai H3,4, Baba T5, Suzuki T1, Koike C1, Tateishi Y1, Tajiri M4, Takemura T6, Ogura T5, Masuda M3, Ohashi K1.
    • Journal Title

      Histol Histopathol

      Volume: 34(11) Pages: 1243-1254

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A subpopulation of airway epithelial cells that express hepatocyte nuclear factor 4α - its implication in the development of non-terminal respiratory unit-type lung adenocarcinoma.2019

    • Author(s)
      Okudela K1, Arai H2, Kitamura H3, Baba T3, Mitsui H4, Suzuki T4, Sugiyama M5, Honda E5, Matsumura M4, Takemura T5, Kataoka T4, Koike C4, Tateshi Y4, Tajiri M2, Ogura T3, Ohashi K4.
    • Journal Title

      Histol Histopathol

      Volume: 34(11) Pages: 1217-1227

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pulmonary melanocytic nevus ? A case report with a mutation analysis of common driver oncogenes2019

    • Author(s)
      Tanaka Meiro、Matsumura Mai、Okudela Koji、Mitsui Hideaki、Tateishi Yoko、Umeda Shigeaki、Suzuki Takehisa、Koike Chihiro、Kataoka Toshiaki、Kawano Naomi、Kojima Yui、Osawa Hiroyuki、Ohashi Kenichi
    • Journal Title

      Pathology International

      Volume: 69 Issue: 11 Pages: 667-671

    • DOI

      10.1111/pin.12850

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] A subpopulation of airway epithelial cells that express hepatocyte nuclear factor 4α - its implication in the development of non-terminal respiratory unit-type lung adenocarcinoma2019

    • Author(s)
      Okudela K, Arai H, Kitamura H, Baba T, Mitsui H, Suzuki T, Sugiyama M, Honda E, Matsumura M, Takemura T, Kataoka T, Koike C, Tateshi Y, Tajiri M, Ogura T, Ohashi K
    • Journal Title

      Histology and histopathology

      Volume: 印刷中

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Secondary pulmonary alveolar proteinosis predominant in the transplanted lung in patients with idiopathic interstitial pneumonia: an autopsy case2018

    • Author(s)
      Ikeda Satoshi、Sekine Akimasa、Baba Tomohisa、Katano Takuma、Yamakawa Hideaki、Oda Tsuneyuki、Iwasawa Tae、Matsumura Mai、Takemura Tamiko、Ogura Takashi
    • Journal Title

      Journal of Thoracic Disease

      Volume: 10 Issue: 5 Pages: E351-E354

    • DOI

      10.21037/jtd.2018.04.49

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A molecular pathological study of four cases of ciliated muconodular papillary tumors of the lung.2018

    • Author(s)
      Kataoka T, Okudela K, Matsumura M, Mitsui H, Suzuki T, Koike C, Sawazumi T, Umeda S, Tateishi Y, Yamanaka S, Ishikawa Y, Arai H, Tajiri M, Ohashi K.
    • Journal Title

      Pathol Int

      Volume: 68 Issue: 6 Pages: 353-358

    • DOI

      10.1111/pin.12664

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Identification of somatic mutations promoting progression of EGFR-mutated adenocarcinoma2021

    • Author(s)
      松村舞依
    • Organizer
      第110回日本病理学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Pathological verification of Oncomine Dx Target Test in non-small cell lung carcinoma2021

    • Author(s)
      松村舞依
    • Organizer
      第62回日本肺癌学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] クライオバイオプシーによる間質性肺炎の診断 びまん性肺疾患の病理診断におけるクライオ生検の現状.2021

    • Author(s)
      松村 舞依
    • Organizer
      第39回日本画像医学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 非小細胞肺がんにおけるオンコマインDx 検査の現状.2020

    • Author(s)
      松村 舞依
    • Organizer
      第109 回日本病理学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] びまん性肺疾患の病理診断におけるクライオ生検の現状2020

    • Author(s)
      松村舞依
    • Organizer
      第39回日本画像医学会
    • Related Report
      2019 Research-status Report
  • [Presentation] EGFR肺腺癌の微小乳頭状組織亜型に特徴的な体細胞遺伝子変異の解明2019

    • Author(s)
      Mai Matsumura, Koji Okudela, Chihiro Koike, Jun Nakabayashi, Hideaki Mitsui, Takehisa Suzuki, Toshiaki Kataoka, Shigeaki Umeda, Yoko Tateishi, Hiromasa Arai, Kenichi Ohashi
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Somatic mutations specific to micropapillary element in EGFR-mutated lung adenocarcinoma2019

    • Author(s)
      Mai Matsumura, Koji Okudela, Chihiro Koike, Jun Nakabayashi, Hideaki Mitsui, Takehisa Suzuki, Toshiaki Kataoka, Shigeaki Umeda, Yoko Tateishi, Hiromasa Arai, Kenichi Ohashi
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] びまん性肺疾患の病理診断におけるクライオ生検と外科的生検の比較2019

    • Author(s)
      松村 舞依
    • Organizer
      第38回日本画像医学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Relationship between MUC21 expression and glycosylation status in EGFR-mutated lung adenocarcinoma2018

    • Author(s)
      Mai Matsumura, Koji Okudela, Hideaki Mitsui, Kaori Denda-Nagai, Hiromasa Arai, Shigeaki Umeda, Yoko Tateishi, Shoji Yamanaka, Tatsuro Irimura, Kenichi Ohashi
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Research-status Report

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

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