Detection of “oncometabolite” 2-hydroxyglutarate by magnetic resonance analysis as a biomarker of IDH1/2 mutations in glioma

• Type of Material: Article
• Authors: Juliya Kalinina, Emory University; Anne Carroll, Emory University; Liya Wang, Emory University; Qiqi Yu, Emory University; Danny E. Mancheno, Emory University; Shaoxiong Wu, Emory University; Frank Liu, Emory University; Jun Ahn, Emory University; Miao He, Emory University; Hui Mao, Emory University; Erwin Van Meir, Emory University
• Language: English
• Date: 2012-10-01
• Publisher: Oxford University Press (OUP): Policy B - Oxford Open Option F
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © Springer-Verlag 2012.
• Final Published Version (URL): http://dx.doi.org/10.1007/s00109-012-0888-x
• Title of Journal or Parent Work: Neuro-Oncology
• ISSN: 1522-8517
• Volume: 14
• Issue: 10
• Start Page: 13
• End Page: 14
• Grant/Funding Information: Grant support This work was supported in part by NIH grants R01 CA86335 and CA116804 (to EGVM), R21AG032104-01A1 and P50CA128301-020003 (to HM), P30 CA138292 (to the Emory Winship Cancer Institute), NINDS Training Grant 2T32NS007480-11 (to JK and Allan I. Levey), a joint Translational Research Pilot Grant from the Winship Cancer Institute and the Atlanta Clinical & Translational Science Instite (ACTSI, UL1RR025008; to HM and EGVM), the Brain Tumor Funders Collaborative (to EGVM), and the Georgia Cancer Coalition (to JK and EGVM).
• Keywords: Oncology; Science & Technology; Life Sciences & Biomedicine; Neurosciences & Neurology; Clinical Neurology
• Research Categories: Health Sciences, Oncology; Biology, Neuroscience

Abstract

Somatic mutations in isocitrate dehydrogenase (IDH)1 and 2 have been identified in a subset of gliomas, rendering these tumors with elevated levels of "oncometabolite," D-2-hydroxyglutarate (2HG). Herein, we report that 2HG can be precisely detected by magnetic resonance (MR) in human glioma specimens and used as a reliable biomarker to identify this subset of tumors. Specifically, we developed a two-dimensional correlation spectroscopy resonance method to reveal the distinctive cross-peak pattern of 2HG in the complex metabolite nuclear MR spectra of brain tumor tissues. This study demonstrates the feasibility, specificity, and selectivity of using MR detection and quantification of 2HG for the diagnosis and classification of IDH1/2 mutation-positive brain tumors. It further opens up the possibility of developing analogous non-invasive MR-based imaging and spectroscopy studies directly in humans in the neuro-oncology clinic.