Journal of Molecular Medicine

, Volume 90, Issue 10, pp 1161–1171

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

Authors

  • Juliya Kalinina
    • Department of NeurosurgeryEmory University
  • Anne Carroll
    • Department of Radiology and Imaging Sciences, Emory Center for Systems ImagingEmory University
  • Liya Wang
    • Department of Radiology and Imaging Sciences, Emory Center for Systems ImagingEmory University
  • Qiqi Yu
    • Department of Radiology and Imaging Sciences, Emory Center for Systems ImagingEmory University
  • Danny E. Mancheno
    • Department of ChemistryEmory University
  • Shaoxiong Wu
    • Department of ChemistryEmory University
  • Frank Liu
    • Department of ChemistryEmory University
  • Jun Ahn
    • Department of Human GeneticsEmory University
  • Miao He
    • Department of Human GeneticsEmory University
    • Department of Radiology and Imaging Sciences, Emory Center for Systems ImagingEmory University
    • Winship Cancer InstituteEmory University
    • Department of NeurosurgeryEmory University
    • Department of Hematology and Medical Oncology, School of MedicineEmory University
    • Winship Cancer InstituteEmory University
Original Article

DOI: 10.1007/s00109-012-0888-x

Cite this article as:
Kalinina, J., Carroll, A., Wang, L. et al. J Mol Med (2012) 90: 1161. doi:10.1007/s00109-012-0888-x

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.

Keywords

Cancer2-HydroxyglutarateIsocitrate dehydrogenaseNuclear magnetic resonanceBiomarker

Supplementary material

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High resolution image file (TIFF 19653 kb)
109_2012_888_MOESM2_ESM.tif (20.3 mb)
High resolution image file (TIFF 20797 kb)

Copyright information

© Springer-Verlag 2012