Inhibition of mutant IDH1 decreases D-2-HG levels without affecting tumorigenic properties of chondrosarcoma cell lines

作者：Johnny Suijker, Jan Oosting, Annemarie Koornneef, Eduard A. Struys, Gajja Sophi Salomons, Frank G. Schaap, Cathelijn J. F. Waaijer, Pauline M. Wijers‐Koster, Inge H. Briaire‐de Bruijn, Lizette C. J. M. Haazen, Scott M. Riester, Amel Dudakovic, Erik H.J. Danen, Anne‐Marie Cleton-Jansen, André J. van Wijnen, Judith V.M.G. Bovée · 发表于：Oncotarget · 年份：2015 · DOI：10.18632/oncotarget.3723 · 被引用次数：109 · 研究领域：Cancer-related molecular mechanisms research、Bone Tumor Diagnosis and Treatments、Sarcoma Diagnosis and Treatment

// Johnny Suijker 1 , Jan Oosting 1 , Annemarie Koornneef 1 , Eduard A. Struys 2 , Gajja S. Salomons 2 , Frank G. Schaap 1 , Cathelijn J.F. Waaijer 1 , Pauline M. Wijers-Koster 1 , Inge H. Briaire-de Bruijn 1 , Lizette Haazen 3 , Scott M. Riester 4 , Amel Dudakovic 4 , Erik Danen 3 , Anne-Marie Cleton-Jansen 1 , Andre J. van Wijnen 4 and Judith V.M.G. Bovée 1 1 Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands 2 Metabolic Unit, Department of Clinical Chemistry, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands 3 Division of Toxicology, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands 4 Department of Orthopedic Surgery, Mayo Clinic, Rochester, NY, USA Correspondence to: Judith V.M.G. Bovée, email: // Keywords : isocitrate dehydrogenase, d-2-hydroxyglutarate, chondrosarcoma, sarcoma, AGI-5198 Received : February 03, 2015 Accepted : March 05, 2015 Published : March 30, 2015 Abstract Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are found in a subset of benign and malignant cartilage tumors, gliomas and leukaemias. The mutant enzyme causes the production of D-2-hydroxyglutarate (D-2-HG), affecting CpG island and histone methylation. While mutations in IDH1/2 are early events in benign cartilage tumors, we evaluated whether these mutations play a role in malignant chondrosarcomas. Compared to IDH1/2 wildtype cell lines, chondrosarcoma cell lines harboring an endogen...