Enrichment technique to allow early detection and monitor emergence of KRAS mutation in response to treatment

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K17508
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: Kitagawa Yoshiyasu 千葉県がんセンター(研究所), 内視鏡科, 医長 (10838577)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: ctDNA

Outline of Final Research Achievements

We developed an enrichment method utilizing pyrrole-imidazole (PI) polyamides and their ability to bind the minor groove of B-DnA. In this study, we investigated the clinical feasibility of incorporating PI polyamides to detect KRAS mutations in ctDNA from pancreatic cancer patients. <Study 1> After enrichment, we performed ctDNA analysis in 14 pancreatic cancer patients with KRAS mutations who underwent surgery at our hospital, but ctDNA was not detected. <Study 2> We performed ctDNA analysis in 21 pancreatic cancer patients and 21 healthy volunteer. After enrichment, no significant difference was observed in the copy number of ctDNA (KRAS G12) between pancreatic cancer patients and healthy volunteer. Therefore, this enrichment technique might be not suitable as a marker for early diagnosis of pancreatic cancer.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

我々は、血液中を循環している微量な腫瘍由来DNA（ctDNA）を濃縮する技術を開発した。本研究では、この濃縮法を用いたctDNA解析が膵臓がん患者の早期発見に役立つか検討を行った。当センターで外科手術を受けたステージⅠ～Ⅲの膵臓がん患者を対象とし、手術前に採取された保存血清を用いて、ctDNA解析を行った。濃縮後にデジタルPCRでctDNAの測定を行ったが、ctDNAは検出されなかった。この濃縮法によるctDNA解析は、膵臓がんの早期発見に寄与しない可能性が示唆された。