Functional analysis of genomic mutations and screening of novel drug, based on comprehensive genomic analysis of muscloskeletal tumors

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H03596
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: National Cancer Center Japan (2018-2019); The University of Tokyo (2017)
• Principal Investigator: Hirata Makoto 国立研究開発法人国立がん研究センター, 中央病院, 医員 (50401071)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 骨軟部腫瘍 / ゲノム解析 / 機能解析

Outline of Final Research Achievements

We have established Japan Sarcoma Genome Consortium to perform genomic analysis or other multi-omics analysis of muscloskeletal tumors, in which progress of clinical and basic research is delayed due to their variety and rarity. Current study aimed identification of putative drugs by performing functional analysis of genomic alterations which were recurrently detected in previous genomic analysis for muscloskeletal tumors.
Based on the previous analysis, several genomic alterations, identified in some histological subtypes including dedifferentiated liposarcoma, tenosynovial giant cell tumor, and chondrosarcoma, were selected for the following functional analysis. Functional in vitro and in vivo analyses were performed in combination with analysis of previous genomic and clinical data. Putative drugs for each histological subtype have been identified in this project.

Free Research Field

Cancer genomics

Academic Significance and Societal Importance of the Research Achievements

骨軟部腫瘍は組織型が多様で希少であることから、他のがん種と比べて分子標的薬などの新規治療薬開発が遅れている。本研究を実施するにあたり、我々は骨軟部腫瘍ゲノムコンソーシアムを立ち上げ、ゲノム解析を中心としたマルチオミックス解析を実施している。しかし、そうしたゲノム解析で検出される遺伝子異常の詳細な機能解析は実施できておらず、その遺伝子異常の病的意義、治療標的としての位置づけは不明であった。本研究ではそうした遺伝子異常について機能解析を行い、治療標的となるシグナル経路、候補薬剤の選定を推進した。今後、本研究で得られた結果が骨軟部腫瘍の新規治療薬開発に向けた基礎データとなることが期待される。