Analysis of age-related genetic changes in non-tumour tissues - Investigating links to mechanisms of cancer-associated fibroblast development

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07133
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Tokyo Medical University
• Principal Investigator: Umezu Tomohiro 東京医科大学, 医学部, 講師 (40385547)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: がん間質 / cell free DNA / mutational signature

Outline of Final Research Achievements

Somatic mutations were extracted from cell free DNA (cfDNA) with the aim of analysing the whole exome between non-tumour and tumour areas using clinical samples and detecting age-related genetic changes in the individual as well as in the cancer stroma. As a result, somatic mutations including VUS were detected not only in cfDNA from cancer patients but also in cfDNA from healthy individuals. In addition, the presence of a mutational signature specific to cfDNA from healthy individuals was confirmed.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究の最大の成果として、非腫瘍組織における加齢に伴って蓄積する遺伝的変化（ゲノムの傷）と、CAFを含むがん微小環境が誘導する発がんとの関与が示唆された。これらの加齢性の体細胞変異を標的とした発がんの超早期診断の開発として、非侵襲性の高いLiquid biospyとしてのcell free DNAから検出できる可能性が示された。今後はがん間質細胞を標的とした新規治療法の開発へと繋げていく。