Comprehensive investigation of tumorigenesis mechanism induced by sarcoma-related fusion genes

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02677
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: National Cancer Center Japan
• Principal Investigator: Kohsaka Shinji 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 (00627119)
• Co-Investigator(Kenkyū-buntansha): 椨 康一 東京医科歯科大学, 難治疾患研究所, 助教 (10466469)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 肉腫 / 融合遺伝子 / 機能解析

Outline of Final Research Achievements

Sarcoma-related fusion genes were integrated into 3T3, C2C12 and mouse mesenchymal stem cells and abilities of cell proliferation and differentiation inhibition were evaluated. Parental cells and oncogenic cells were labeled with individual fluorescent proteins and seeded on polymer slides to identify synthetic polymers on which oncogenic cells grow rapidly or attach strongly compared with parental cells. Established oncogenic cells were performed RNA-seq and conducted clustering analysis and Gene Set Enrichment Analysis to identify gene sets and signaling pathways specifically affected by respective fusion genes. Candidate molecular targeted drugs having specific inhibitory effects on fusion-introduced cells were screened and validated by individual drug sensitivity assay.

Free Research Field

がんゲノム

Academic Significance and Societal Importance of the Research Achievements

融合遺伝子特異的な遺伝子発現パターンが同定され, 融合遺伝子横断的な分類がすすみ, 融合遺伝子を標的とした分子標的薬の創薬に向けた分子プロファイリングの基盤が構築された. また融合遺伝子導入細胞特異的に増殖・接着する合成ポリマーが同定され, がん化や薬剤耐性などの細胞機能のスクリーニングに適したマテリアルの開発につながることが期待される.