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

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 specime...

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Bibliographic Details
Published in:Journal of molecular medicine (Berlin, Germany) Germany), 2012-10, Vol.90 (10), p.1161-1171
Main Authors: Kalinina, Juliya, Carroll, Anne, Wang, Liya, Yu, Qiqi, Mancheno, Danny E., Wu, Shaoxiong, Liu, Frank, Ahn, Jun, He, Miao, Mao, Hui, Van Meir, Erwin G.
Format: Article
Language:English
Subjects:
Adult
Aged
Biological and medical sciences
Biomarkers, Tumor - metabolism
Biomedical and Life Sciences
Biomedicine
Brain Neoplasms - diagnosis
Brain Neoplasms - genetics
Brain Neoplasms - metabolism
Child
Child, Preschool
DNA Mutational Analysis
Female
General aspects
Glioma - diagnosis
Glioma - genetics
Glioma - metabolism
Glutarates - metabolism
Human Genetics
Humans
Internal Medicine
Isocitrate Dehydrogenase - genetics
Magnetic Resonance Spectroscopy - methods
Male
Medical sciences
Middle Aged
Molecular Medicine
Neurology
Original Article
Sensitivity and Specificity
Tumors of the nervous system. Phacomatoses
Young Adult
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Summary: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.
ISSN:0946-2716
1432-1440
DOI:10.1007/s00109-012-0888-x