Identification of individual carcinogenic factors by mutation signature analysis in normal human tissues

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07745
• 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: National Cancer Center Japan
• Principal Investigator: Yamashita Satoshi 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 (80321876)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 変異 / 次世代シーケンサー

Outline of Final Research Achievements

Mutation signatures　have been shown to be associated with exposure to carcinogens, and are important for cancer research. In this study, we have developed a novel ultra-low frequency point mutation frequency analysis method by a next-generation sequencer. It can detect only true mutations in which the same mutation exists in both strands. By using a restriction enzyme, BamHI, efficient analysis with a low read number was realized. A model sample was prepared, and it was used to confirm that the mutation frequency was well correlated with the expected mutation frequency. It was shown that the peripheral blood DNA of pediatric cancer patients after treatment has a mutation signature due to the drug used for the treatment.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により実現した次世代シーケンサーを用いた両ストランドに同一の変異が存在する真の変異のみを検出する新規の超低頻度の点突然変異頻度解析法は効率がよいため、多数の検体の解析が実現可能である。そのため多くの臨床検体、正常組織を用いた解析への応用が今後期待できる。また、寛解後の小児がん患者末梢血DNAには化学治療の程度と相関する変異頻度と、治療に用いた薬剤に起因する変異シグネチャーが認められることを示したことは、治療による二次がん発生と変異との関係を強く示唆するのものあり、今後の多数の検体を用いた解析が期待される。