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

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08392
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Hamamatsu 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
• Keywords: 大腸がん / DNAミスマッチ修復

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.

Free Research Field

消化器内科学

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。