Exploratory research for ccfDNA in Lynch syndrome

• Project/Area Number: 18K07314
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Tokyo Metropolitan Komagome Hospital (Clinical research laboratory)
• Principal Investigator: Yamaguchi Tatsuro 東京都立駒込病院(臨床研究室), 大腸外科, 部長 (10538482)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: リンチ症候群 / ccfDNA / マイクロサテライト不安定性 / ddPCR法

Outline of Final Research Achievements

To evaluate the utility of ccfDNA in the surveillance of Lynch syndrome, microsatellite instability (MSI) in ccfDNA was tested and compared with tumor development. A total of 28 patients with Lynch syndrome were participated after informed consent, and a mean of 2.1 blood samples were collected. We used Promega markers (BAT25, BAT26, NR21, NR24, Mono27) for analyzing MSI by Droplet Digital PCR (ddPCR) method.
MSI was observed in three patients. Of the three patients, one patient had two markers and two patients had one marker abnormality. The mean variant allele frequency (VAF) of the four abnormal markers was 8.6% (0.7%-4.1%). Among three patients with MSI, one had cecal cancer, one had ileal cancer, and one had mediastinal tumor. However, one patient undergoing treatment for lymph node metastasis from gastric cancer had no MSI in ccfDNA.

Academic Significance and Societal Importance of the Research Achievements

ccfDNAに含まれる腫瘍由来のDNA（ctDNA）は、がんの根治性や化学療法などの治療効果の評価への利用が期待されている。リンチ症候群はがんの高危険群であるため、生涯に渡り頻回に内視鏡検査などを受けなければならない。しかし、リンチ症候群のサーベイランスにおけるccfDNA (ctDNA)の有用性が証明されれば、内視鏡検査の間隔を空けることができるなど、患者負担や医療費の減少につながる可能性がある。本研究において、ccfDNAを解析したところMSIを認めた症例全例に腫瘍の発生を認めていた。今後、多施設共同研究で証明する必要があるが、リンチ症候群のサーベイランスに有用であることが示唆された。