• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Actionability of proofreading DNA polymerase in colorectal cancer with proficient DNA mismatch repair system

Research Project

Project/Area Number 19K08392
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Iwaizumi Moriya  浜松医科大学, 医学部, 助教 (60444361)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords大腸がん / DNAミスマッチ修復 / 大腸癌 / 高頻度変異 / DNAポリメラーゼ / 高頻度変異大腸がん / DNAミスマッチ修復機構 / 校正機能評価 / マイクロサテライト不安定性 / 遺伝子診療
Outline of Research at the Start

本研究は、DNAミスマッチ修復機構(MMR)が正常(proficient-MMR: pMMR)でありながら高頻度の変異を呈する大腸がんの臨床・分子遺伝学的特徴を把握し、DNAポリメラーゼ校正機能異常がどのように高頻度の変異を誘導し、大腸がんの発育進展に関与するかを解明することを目的としている。また、DNAポリメラーゼ校正機能異常を呈するpMMR大腸がんの薬物療法感受性変化を検討することにより、今後のさらなる個別化を考えた有効で安全な大腸がん薬物療法や患者・家族ケアの推進に貢献することも目的とする。

Outline of Final Research Achievements

In the present study, the DNA MMR status for stage 0 patients with CRC treated using endoscopic submucosal dissection or endoscopic mucosal resection was analyzed and none of the endoscopically resected specimens exhibited dMMR among the 41 patients diagnosed with stage 0 CRC. A frameshift variant of c.973delA on SGO1 was observed in 16 of the 45 cases that could be evaluated. Its frequency was 35.6%. MSI-H was only 3 cases. Two cases of MSI-H were associated with the SGO1 variant of c.973delA. Approximately 40% of advanced gastric cancers have SGO1 frameshift variants and are not necessarily associated with MSI status. Finally, we detected one germline variant of POLD1, which is classified to variance of unknown significance. After the variant was transfected with human colorectal cancer cell line, we found out the variant did not lead to the phenotype of high-tumor mutation burden.

Academic Significance and Societal Importance of the Research Achievements

研究期間内に、DNAミスマッチ修復機構に異常のない大腸癌の臨床病理学的な特徴が判明した。また、DNAミスマッチ修復機構に異常は認められないが、腫瘍で体細胞変異がおこりやすいがんの頻度や特徴を探ることが可能であった。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (5 results)

All 2021 2020

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (2 results) Book (1 results)

  • [Journal Article] DNA mismatch repair is not disrupted in stage 0 colorectal cancer resected using endoscopic submucosal dissection.2020

    • Author(s)
      Tomohiro Sugiyama, Moriya Iwaizumi, Masanao Kaneko, Shinya Tani, Mihoko Yamade, Yasushi Hamaya, Takahisa Furuta, Hiroaki Miyajima, Satoshi Osawa, Satoshi Baba, Masato Maekawa, Ken Sugimoto
    • Journal Title

      Oncology letters

      Volume: 20(3) Pages: 2435-2441

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Microsatellite frameshift variants in SGO1 of gastric cancer are not always associated with MSI status2020

    • Author(s)
      http://orcid.org/0000-0001-5601-4741Tomohiro Sugiyama, Moriya Iwaizumi, Terumi Taniguchi, Satoshi Suzuki, Shinya Tani, Mihoko Yamade, Yasushi Hamaya, Satoshi Osawa, Takahisa Furuta, Hiroaki Miyajima, Tsutomu Ohta, Satoshi Baba, Haruhiko Sugimura, Masato Maekawa, Ken Sugimoto
    • Journal Title

      Journal of clinical pathology

      Volume: 73 Issue: 6 Pages: 206934-206934

    • DOI

      10.1136/jclinpath-2020-206934

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 内視鏡所見により疑われ診断に至った遺伝性びまん性胃がん家系への遠隔医療と対面医療の比較2021

    • Author(s)
      岩泉守哉、小島梨沙、山田英孝、椙村春彦
    • Organizer
      第27回日本遺伝性腫瘍学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 遺伝医療から遺伝学的解析に至った遺伝性びまん性胃癌診療の経験2021

    • Author(s)
      岩泉守哉、前川真人
    • Organizer
      第68回日本臨床検査医学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Book] 消化器内視鏡2021

    • Author(s)
      岩泉守哉、椙村春彦
    • Total Pages
      3
    • Publisher
      東京医学社
    • Related Report
      2021 Annual Research Report

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi