2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity

• Published in: Science translational medicine Vol. 9; no. 375
• Main Authors: Sulkowski, Parker L, Corso, Christopher D, Robinson, Nathaniel D, Scanlon, Susan E, Purshouse, Karin R, Bai, Hanwen, Liu, Yanfeng, Sundaram, Ranjini K, Hegan, Denise C, Fons, Nathan R, Breuer, Gregory A, Song, Yuanbin, Mishra-Gorur, Ketu, De Feyter, Henk M, de Graaf, Robin A, Surovtseva, Yulia V, Kachman, Maureen, Halene, Stephanie, Günel, Murat, Glazer, Peter M, Bindra, Ranjit S
• Format: Journal Article
• Language: English
• Published: United States 01.02.2017
• Subjects: Animals; Cell Line, Tumor; DNA Breaks, Double-Stranded; DNA Repair; Female; Glioma - drug therapy; Glioma - genetics; Glutarates - pharmacology; Homologous Recombination; Humans; Isocitrate Dehydrogenase - genetics; Isocitrate Dehydrogenase - pharmacology; Mice, Nude; Poly(ADP-ribose) Polymerase Inhibitors - pharmacology; Xenograft Model Antitumor Assays

2-Hydroxyglutarate (2HG) exists as two enantiomers, (R)-2HG and (S)-2HG, and both are implicated in tumor progression via their inhibitory effects on α-ketoglutarate (αKG)-dependent dioxygenases. The former is an oncometabolite that is induced by the neomorphic activity conferred by isocitrate dehyd...