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Non-invasive detection of 2-hydroxyglutarate and other metabolites in IDH1 mutant glioma patients using magnetic resonance spectroscopy
Open accessAbstract
Mutations of the isocitrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) are commonly found in primary brain cancers. We previously reported that a novel enzymatic activity of these mutations results in the production of the putative oncometabolite, R(-)-2-hydroxyglutarate (2-HG). Here we investigated the ability of magnetic resonance spectroscopy (MRS) to detect 2-HG production in order to non-invasively identify patients with IDH1 mutant brain tumors. Patients with intrinsic glial brain tumors (n = 27) underwent structural and spectroscopic magnetic resonance imaging prior to surgery. 2-HG levels from MRS data were quantified using LC-Model software, based upon a simulated spectrum obtained from a GAMMA library added to the existing prior knowledge database. The resected tumors were then analyzed for IDH1 mutational status by genomic DNA sequencing, Ki-67 proliferation index by immunohistochemistry, and concentrations of 2-HG and other metabolites by liquid chromatography-mass spectrometry (LC-MS). MRS detected elevated 2-HG levels in gliomas with IDH1 mutations compared to those with wild-type IDH1 (P = 0.003). The 2-HG levels measured in vivo with MRS were significantly correlated with those measured ex vivo from the corresponding tumor samples using LC-MS (r (2) = 0.56; P = 0.0001). Compared with wild-type tumors, those with IDH1 mutations had elevated choline (P = 0.01) and decreased glutathione (P = 0.03) on MRS. Among the IDH1 mutated gliomas, quantitative 2-HG values were correlated with the Ki-67 proliferation index of the tumors (r ( 2 ) = 0.59; P = 0.026). In conclusion, water-suppressed proton ((1)H) MRS provides a non-invasive measure of 2-HG in gliomas, and may serve as a potential biomarker for patients with IDH1 mutant brain tumors. In addition to 2-HG, alterations in several other metabolites measured by MRS correlate with IDH1 mutation status.
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“recent data have suggested that 1H magnetic resonance spectroscopy can be applied for 2HG detection in vivo for glioma (Andronesi et al., 2012; Choi et al., 2012; Gross et al., 2010; Pope et al., 2012)”
From Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate (2012) · cites this paper as Pope et al., 2012
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Metadata
- Authors
- Pope, W. B., Prins, R. M., Albert Thomas, M., Nagarajan, R., Yen, K. E., Bittinger, M. A., Salamon, N., Chou, A. P., Yong, W. H., Soto, H., Wilson, N., Driggers, E., Jang, H. G., Su, S. M., Schenkein, D. P., Lai, A., Cloughesy, T. F., Kornblum, H. I., Wu, H., Fantin, V. R., & Liau, L. M.
- Affiliations
- University of California, Los Angeles (US)
- Agios Pharmaceuticals (United States) (US)
- Corresponding author
- Liau, Linda M.
- ORCID
- Venue
- Journal of Neuro-Oncology
- Published
- 2011-10-21
- Volume
- 107
- Issue
- 1
- Pages
- 197-205
- ISSN
- 0167-594X (ISSN-L)
- 1573-7373
- PMC
- PMC3650613
- OpenAlex
- W2083820071
- Cited by
- 318
- References
- 32
- Citations by year
- 2026: 14 · 2025: 8 · 2024: 12 · 2023: 22 · 2022: 15 · 2021: 23 · 2020: 26 · 2019: 27 · 2018: 27 · 2017: 32 · 2016: 29 · 2015: 27 · 2014: 24 · 2013: 17 · 2012: 13
- FWCI
- 8.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neuro-Oncology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000124)
- National Cancer Institute (R01CA121131, R01CA123396, K01CA111402, R01CA112358)
- National Institute of Neurological Disorders and Stroke (R01NS052563)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- 2-hydroxyglutarate, IDH1 mutation, glioma, oncometabolites, magnetic resonance spectroscopy, non-invasive cancer detection, choline, glutathione, Ki-67 proliferation index, tumor metabolites, biomarkers
- MeSH terms
- Adult, Aged, Aged, 80 and over, Brain Neoplasms, Chromatography, Liquid, DNA, Neoplasm, Female, Follow-Up Studies, Glioma, Glutarates, Humans, Isocitrate Dehydrogenase, Magnetic Resonance Imaging, Male, Middle Aged, Mutation, Magnetic Resonance Spectroscopy, Prognosis, Prospective Studies, Mass Spectrometry, Biomarkers, Tumor, Polymerase Chain Reaction, Young Adult
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