Development of a novel liquid biopsy to monitor DNA demethylation

• Project/Area Number: 18K07989
• 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: National Cancer Center Japan
• Principal Investigator: Takeshima Hideyuki 国立研究開発法人国立がん研究センター, 研究所, ユニット長 (40432497)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: エピジェネティクス / リキッドバイオプシー / がん治療 / エピジェネティック治療 / DNAメチル化

Outline of Final Research Achievements

In this study, we aimed to develop a novel liquid biopsy to monitor DNA demethylation after the treatment with a DNA demethylating drug by focusing on the fact that heavily methylated genomic regions in cancer cells could be secreted as cell-free DNA. 959 genes heavily methylated in gastric cancer cells were demethylated 40% or more by the treatment with a DNA demethylating drug. Among these genes, 46 genes were re-expressed. These genes are considered to be useful for monitoring of demethylation using cfDNA.

Academic Significance and Societal Importance of the Research Achievements

現在、脱メチル化剤治療の固形がんへの応用に向けた臨床試験が精力的に展開されている。本研究で得られた候補遺伝子は、固形がんにおける脱メチル化剤治療の効果モニターに応用できる可能性がある。このようなバイオマーカーを用いた脱メチル化の高感度なリキッドバイオプシーの確立は、固形がんに対する脱メチル化剤治療の臨床導入を加速すると考えられる。