Actionability of proofreading DNA polymerase in colorectal cancer with proficient DNA mismatch repair system
| Project/Area Number |
19K08392
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| 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)
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| 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 |
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| 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。
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| 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.
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| 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。
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Report
(4 results)
Research Products
(5 results)
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[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
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Journal Title
Oncology letters
Volume: 20(3)
Pages: 2435-2441
Related Report
Peer Reviewed / Open Access
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[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
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Journal Title
Journal of clinical pathology
Volume: 73
Issue: 6
Pages: 206934-206934
DOI
Related Report
Peer Reviewed / Open Access
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