Original Article

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

  • Juliya KalininaAffiliated withDepartment of Neurosurgery, Emory University
  • , Anne CarrollAffiliated withDepartment of Radiology and Imaging Sciences, Emory Center for Systems Imaging, Emory University
  • , Liya WangAffiliated withDepartment of Radiology and Imaging Sciences, Emory Center for Systems Imaging, Emory University
  • , Qiqi YuAffiliated withDepartment of Radiology and Imaging Sciences, Emory Center for Systems Imaging, Emory University
  • , Danny E. ManchenoAffiliated withDepartment of Chemistry, Emory University
  • , Shaoxiong WuAffiliated withDepartment of Chemistry, Emory University
  • , Frank LiuAffiliated withDepartment of Chemistry, Emory University
  • , Jun AhnAffiliated withDepartment of Human Genetics, Emory University
  • , Miao HeAffiliated withDepartment of Human Genetics, Emory University
    • , Hui MaoAffiliated withDepartment of Radiology and Imaging Sciences, Emory Center for Systems Imaging, Emory UniversityWinship Cancer Institute, Emory University Email author 
    • , Erwin G. Van MeirAffiliated withDepartment of Neurosurgery, Emory UniversityDepartment of Hematology and Medical Oncology, School of Medicine, Emory UniversityWinship Cancer Institute, Emory University Email author 

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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

Cancer 2-Hydroxyglutarate Isocitrate dehydrogenase Nuclear magnetic resonance Biomarker