Investigation of functional roles of mutant IDH as specific mutations in cartilage-forming tumors and its application for the development of treatment

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04956
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kyoto University
• Principal Investigator: Toguchida Junya 京都大学, ウイルス・再生医科学研究所, 教授 (40273502)
• Co-Investigator(Kenkyū-buntansha): 金 永輝 京都大学, 医学研究科, 特定助教 (90620344) ; 岡本 健 京都大学, 医学研究科, 准教授 (30414113) ; 池谷 真 京都大学, iPS細胞研究所, 准教授 (20442923)
• Co-Investigator(Renkei-kenkyūsha): Watanabe Akira 京都大学, iPS細胞研究所, 特定拠点助教 (60506765)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: chondrosarcoma / IDH / iPSC / p16

Outline of Final Research Achievements

Mutations of IDH gene are driver mutations in cartilage-forming tumors. To understand the mechanism of tumor specificity and functional role of IDH mutations in tumorigenesis of cartilage-forming tumors, we have performed experiments using human iPS cells. We established iPS cells with a drug-inducible mutant IDH gene in the AAVS1 locus and induced the expression of mutant IDH after the differentiation into mesenchymal stem cells (MSC). As a result, we have observed that mutant IDH has an inhibitor effect for the growth of MSC and as for the effects on differentiation, it inhibited osteogenesis and promoted the expression of cartel-related genes. To recapitulate the tumorigenesis in vitro, we further introduced the knock-out type mutations of p16 gene as a passenger mutation into IDH-AAVS-iPSCs and investigated the tumor forming capacity of iMSCs with mutant IDH and without p16 gene.

Free Research Field

幹細胞生物学、整形外科学