Study of somatic mutations in normal blood cells using whole-genome sequencing

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20840
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: National Cancer Center Japan
• Principal Investigator: Yoshida Kenichi 国立研究開発法人国立がん研究センター, 研究所, 分野長 (50738226)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 正常血液細胞

Outline of Final Research Achievements

In this study, we aimed to reveal the accumulation of somatic mutations in normal blood cells and its relationship with aging and environmental factors, such as alcohol drinking and smoking, for the further understanding of the mechanisms of development of hematological malignancies. We collected peripheral blood samples from one hundred healthy donors who visited medical checkup and selected the cases who will be subjected to the genetic studies based on their age and smoking and drinking histories. We performed whole-genome sequencing of 174 single-cell blood cell colonies derived from one cord blood sample and 11 healthy donors. As a result, 14 mutations accumulated per year in normal blood cells, which was consistent with the previous reports. There was also a heterogeneity of mutation burden between individuals, which might be related with life history of the donors.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では日本人の正常血液細胞における加齢や環境因子による体細胞変異の蓄積の全貌が明らかになったが、このデータは今後全ゲノム解析などにより日本人における骨髄性腫瘍の発症の機序を明らかにする上で重要なデータとなると考えられる。また、本研究で健常人から得られたデータは今後、様々な造血器腫瘍に対するがん感受性を有する疾患における血液細胞の研究においても重要なコントロールデータとなると考えられ、学術的な意義が大きい。さらに、今後の研究で血液細胞における体細胞変異の蓄積における個人差や造血器腫瘍発症のリスクと生活習慣との関係が明らかになれば、社会的意義も大きいと考えられる。