Magnetic resonance of 2-hydroxyglutarate in IDH1-mutated low-grade gliomas

Recent studies have indicated that a significant survival advantage is conferred to patients with gliomas whose lesions harbor mutations in the genes isocitrate dehydrogenase 1 and 2 (IDH1/2). IDH1/2 mutations result in aberrant enzymatic production of the potential oncometabolite D-2-hydroxyglutara...

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Bibliographic Details
Published in:Science translational medicine 2012-01, Vol.4 (116), p.116ra5-116ra5
Main Authors: Elkhaled, Adam, Jalbert, Llewellyn E, Phillips, Joanna J, Yoshihara, Hikari A I, Parvataneni, Rupa, Srinivasan, Radhika, Bourne, Gabriela, Berger, Mitchel S, Chang, Susan M, Cha, Soonmee, Nelson, Sarah J
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Base Sequence
Brain Neoplasms - enzymology
Brain Neoplasms - genetics
Brain Neoplasms - metabolism
Brain Neoplasms - surgery
Brain tumors
Data processing
Diffusion
DNA Mutational Analysis
Glioma
Glioma - enzymology
Glioma - genetics
Glioma - metabolism
Glioma - surgery
Glutarates - metabolism
Humans
Immunohistochemistry
Isocitrate dehydrogenase
Isocitrate Dehydrogenase - chemistry
Isocitrate Dehydrogenase - genetics
Magnetic Resonance Spectroscopy - methods
Metabolites
Molecular Sequence Data
Mutation
Mutation - genetics
N.M.R
Neoplasm Grading
Phantoms, Imaging
Protons
Spectroscopy
Spinning
Survival
Translation
Tumors
World Health Organization
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Summary:Recent studies have indicated that a significant survival advantage is conferred to patients with gliomas whose lesions harbor mutations in the genes isocitrate dehydrogenase 1 and 2 (IDH1/2). IDH1/2 mutations result in aberrant enzymatic production of the potential oncometabolite D-2-hydroxyglutarate (2HG). Here, we report on the ex vivo detection of 2HG in IDH1-mutated tissue samples from patients with recurrent low-grade gliomas using the nuclear magnetic resonance technique of proton high-resolution magic angle spinning spectroscopy. Relative 2HG levels from pathologically confirmed mutant IDH1 tissues correlated with levels of other ex vivo metabolites and histopathology parameters associated with increases in mitotic activity, relative tumor content, and cellularity. Ex vivo spectroscopic measurements of choline-containing species and in vivo magnetic resonance measurements of diffusion parameters were also correlated with 2HG levels. These data provide extensive characterization of mutant IDH1 lesions while confirming the potential diagnostic value of 2HG as a surrogate marker of patient survival. Such information may augment the ability of clinicians to monitor therapeutic response and provide criteria for stratifying patients to specific treatment regimens.
ISSN:1946-6234
1946-6242
DOI:10.1126/scitranslmed.3002796