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A study for mechanisms that maintain the genomic integration in lung cancer with chromosomal instability

Research Project

Project/Area Number 18K08791
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55040:Respiratory surgery-related
Research InstitutionNational Hospital Organization, Kyushu Cancer Center (2020)
Oita University (2018-2019)

Principal Investigator

Okamoto Tatsuro  独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他部局等, 呼吸器腫瘍科部長 (80568626)

Co-Investigator(Kenkyū-buntansha) 宮脇 美千代  大分大学, 医学部, 講師 (30404388)
杉尾 賢二  大分大学, 医学部, 教授 (70235927)
小副川 敦  大分大学, 医学部, 准教授 (90432939)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords肺癌 / EGFR遺伝子変異 / 腫瘍内不均一性 / 進化的発育 / ゲノム不安定性 / 多領域クラスタリング解析 / 多領域RNAシーケンス
Outline of Final Research Achievements

Focusing on MDM2 gene that had shown a copy number alteration similar to that of EGFR gene in the intratumor heterogeneity, we investigated the significance of MDM2 gene expression in EGFR mutation-positive lung cancer. In addition, based on the findings suggestive of evolutionary growth in EGFR mutation-positive lung cancer on preoperative CT images, tumors were classified according to the developmental stage. Comprehensive gene mutation analyses were done by next-generation sequencing of EGFR lung cancer samples by the developmental stage, and genetic changes important for the acquisition of malignant traits were examined. These results suggested that EGFR mutation-positive lung cancer may have altered cell composition within the tumor during the evolutionary development.

Academic Significance and Societal Importance of the Research Achievements

ドライバー遺伝子変異の代表格であるEGFR遺伝子変異は日本人に発生する肺腺癌の約半数に認められる。臨床肺癌においては、EGFR変異を有する腫瘍は発生初期では低悪性であるが、癌の進化的発育過程において高悪性の性質に変化することが示唆されている。EGFR遺伝子変異肺腺癌においても、腫瘍内不均一性が認められており、これが薬剤耐性に関与する可能性が報告されている。本研究は、肺癌の腫瘍内不均一性を生むと考えられる、がん関連遺伝子変化を明らかにすることで、肺癌細胞の生存に不可欠なゲノム維持機構の同定に繋げることを目的とした基盤的研究である。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (3 results)

All 2020 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (2 results)

  • [Journal Article] Prognostic Impact of Smoking Period in Patients with Surgically Resected Non-small Cell Lung Cancer2020

    • Author(s)
      Takamori Shinkichi、Shimokawa Mototsugu、Matsubara Taichi、Haratake Naoki、Toyozawa Ryo、Miura Naoko、Yamaguchi Masafumi、Seto Takashi、Tagawa Tetsuzo、Okamoto Tatsuro、Takenoyama Mitsuhiro、Maehara Yoshihiko、Mori Masaki
    • Journal Title

      Annals of Surgical Oncology

      Volume: 28 Issue: 2 Pages: 685-694

    • DOI

      10.1245/s10434-020-08851-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] EGFR陽性肺腺癌の進化的発育における遺伝子変化の検討2019

    • Author(s)
      岡本龍郎、野田大樹、辛島髙志、安部美幸、内匠陽平、 阿南健太郎、宮脇美千代、武内秀也、杉尾賢二
    • Organizer
      第60回日本肺癌学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 肺腺癌切除例におけるEGFR遺伝子変異癌の画像的特徴と予後2019

    • Author(s)
      岡本 龍郎、辛島 高志、安部 美幸、内匠 陽平、橋本 崇史、宮脇 美千代、武内 秀也、杉尾 賢二
    • Organizer
      日本外科学会定期学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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