Modeling fusion gene-associated bone and soft tissue sarcoma and its application to therapies

2016 Fiscal Year Final Research Report

• Project/Area Number: 26250029
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: Nakamura Takuro 公益財団法人がん研究会, がん研究所 発がん研究部, 部長 (00180373)
• Co-Investigator(Kenkyū-buntansha): 森 誠一 公益財団法人がん研究会, その他部局等, 研究員 (10334814) ; 黒田 雅彦 東京医科大学, 医学部, 教授 (80251304)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 発がん / 融合遺伝子 / 骨軟部肉腫 / 動物モデル / 発生母地 / 転移 / 微小環境 / 協調遺伝子

Outline of Final Research Achievements

It has been challenging to create fusion gene-associated bone and soft tissue sarcoma. We have generated mouse models for Ewing sarcoma, alveolar soft part sarcoma, CIC-DUX4 sarcoma and synovial sarcoma, and established the ex vivo model system of sarcoma. These four models recapitulate phenotypes of human sarcoma in morphology, gene expression and biological characteristics. Using the models, cell-of-origin of Ewing sarcoma, molecular mechanisms of hematogenous metastasis in alveolar soft part sarcoma, novel biomarkers for CIC-DUX4 sarcoma and cooperative genes of SYT-SSX1 in synovial sarcoma development have been clarified. Therapeutic effects of inhibitors and anti-cancer drugs were evaluated in vitro and in vivo using Ewing sarcoma and CIC-DUX4 sarcoma models.

Free Research Field

分子腫瘍学