CANCER BIOLOGY: Edited by Pierre Hainaut and Amelie PlymothAltered cancer cell metabolism in gliomas with mutant IDH1 or IDH2Borodovsky, Alexandra; Seltzer, Meghan J.; Riggins, Gregory J. Author Information Ludwig Collaborative Laboratory, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Correspondence to Gregory J. Riggins, MD, PhD, Ludwig Collaborative Laboratory, Department of Neurosurgery, Johns Hopkins University, Koch Building Room 257, 1550 Orleans Street, Baltimore, MD 21231, USA. Tel: +1 410 502 2905; fax: +1 410 502 5559; e-mail: [email protected] Current Opinion in Oncology: January 2012 - Volume 24 - Issue 1 - p 83-89 doi: 10.1097/CCO.0b013e32834d816a Buy Metrics Abstract Purpose of review IDH1/2 mutations occur in up to 70% of low-grade gliomas and secondary glioblastomas. Mutation of these enzymes reduces the wildtype function of the enzyme (conversion of isocitrate to α-ketoglutarate) while conferring a new enzymatic function, the production of D-2-hydroxyglutarate (D-2-HG) from α-ketoglutarate (α-KG). However, it is unclear how these enzymatic changes contribute to tumorigenesis. Here, we discuss the recent studies that demonstrate how IDH1/2 mutation may alter the metabolism and epigenome of gliomas, how these changes may contribute to tumor formation, and opportunities they might provide for molecular targeting. Recent findings Metabolomic studies of IDH1/2 mutant cells have revealed alterations in glutamine, fatty acid, and citrate synthesis pathways. Additionally, D-2-HG produced by IDH1/2 mutant cells can competitively inhibit α-KG-dependent enzymes, including histone demethylases and DNA hydroxylases, potentially leading to a distinct epigenetic phenotype. Alterations in metabolism and DNA methylation present possible mechanisms of tumorigenesis. Summary Recent attempts to improve outcomes for glioma patients have resulted in incremental gains. Studies of IDH1/2 mutations have provided mechanistic insights into tumorigenesis and potential avenues for therapeutic intervention. Further study of IDH1/2 mutations might allow for improved therapeutic strategies. © 2012 Lippincott Williams & Wilkins, Inc.