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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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Cites
Verhaak, R. G. W., Hoadley, K. A., Purdom, E., Wang, V., Qi, Y., Wilkerson, M. D., Miller, C. R., Ding, L., Golub, T., Mesirov, J. P., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.020 · Cited by 7,575
An Integrated Genomic Analysis of Human Glioblastoma Multiforme
Parsons, D. W., Jones, S., Zhang, X., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Siu, I.-M., Gallia, G. L., et al. (2008) · Science · doi:10.1126/science.1164382 · Cited by 5,857
IDH1 and IDH2 Mutations in Gliomas
Yan, H., Parsons, D. W., Jin, G., McLendon, R., Rasheed, B. A., Yuan, W., Kos, I., Batinic-Haberle, I., Jones, S., Riggins, G. J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808710 · Cited by 5,847
Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
Dang, L., White, D. W., Gross, S., Bennett, B. D., Bittinger, M. A., Driggers, E. M., Fantin, V. R., Jang, H. G., Jin, S., Keenan, M. C., et al. (2009) · Nature · doi:10.1038/nature08617 · Cited by 4,154
Self-citationEstimation of metabolite concentrations from localized in vivo proton NMR spectra
Provencher, S. W. (1993) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910300604 · Cited by 3,659
Xu, W., Yang, H., Liu, Y., Yang, Y., Wang, P., Kim, S.-H., Ito, S., Yang, C., Wang, P., Xiao, M.-T., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2010.12.014 · Cited by 2,875
WISEMAN, H., & HALLIWELL, B. (1996) · Biochemical Journal · doi:10.1042/bj3130017 · Cited by 2,345
Ward, P. S., Patel, J., Wise, D. R., Abdel-Wahab, O., Bennett, B. D., Coller, H. A., Cross, J. R., Fantin, V. R., Hedvat, C. V., Perl, A. E., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.01.020 · Cited by 2,020
Self-citationSpatial Localization in NMR Spectroscopy in Vivo
Bottomley, P. A. (1987) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1987.tb32915.x · Cited by 1,382
Hartmann, C. J., Meyer, J., Balß, J., Capper, D., Mueller, W. C., Christians, A., Felsberg, J., Wolter, M., Mawrin, C., Wick, W., et al. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0561-9 · Cited by 1,163
Analysis of the IDH1 codon 132 mutation in brain tumors
Balss, J., Meyer, J., Mueller, W., Korshunov, A., Hartmann, C., & von Deimling, A. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0455-2 · Cited by 1,036
IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas
Watanabe, T., Nobusawa, S., Kleihues, P., & Ohgaki, H. (2009) · The American Journal of Pathology · doi:10.2353/ajpath.2009.080958 · Cited by 1,027
Gross, S., Cairns, R. A., Minden, M. D., Driggers, E. M., Bittinger, M. A., Jang, H. G., Sasaki, M., Jin, S., Schenkein, D. P., Su, S. M., et al. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20092506 · Cited by 736
Self-citationWET, a T1- and B1-Insensitive Water-Suppression Method for in Vivo Localized 1H NMR Spectroscopy
Ogg, R. J., Kingsley, R. B., & Taylor, J. S. (1994) · Journal of Magnetic Resonance Series B · doi:10.1006/jmrb.1994.1048 · Cited by 734
Computer Simulations in Magnetic Resonance. An Object-Oriented Programming Approach
Smith, S. A., Levante, T. O., Meier, B. H., & Ernst, R. R. (1994) · Journal of Magnetic Resonance Series A · doi:10.1006/jmra.1994.1008 · Cited by 711
Profiling the effects of isocitrate dehydrogenase 1 and 2 mutations on the cellular metabolome
Reitman, Z. J., Jin, G., Karoly, E. D., Spasojevic, I., Yang, J., Kinzler, K. W., He, Y., Bigner, D. D., Vogelstein, B., & Yan, H. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019393108 · Cited by 449 · cited 9×
“High-throughput sequencing previously revealed that the metabolic enzymes, IDH1 and IDH2, are frequently mutated in a majority of several types of malignant gliomas [4, 5].”
InfluentialIDH mutations in glioma and acute myeloid leukemia
Dang, L., Jin, S., & Su, S.-S. M. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.07.002 · Cited by 385
Self-citationvan den Bent, M. J., Dubbink, H. J., Marie, Y., Brandes, A. A., TAPHOORN, M. J. B., Wesseling, P., Frénay, M., Tijssen, C. C., Lacombe, D. A., Idbaïh, A., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-2902 · Cited by 384
Dowling, C., Bollen, A. W., Noworolski, S. M., McDermott, M. W., Barbaro, N. M., Day, M. R., Henry, R. G., Chang, S. M., Dillon, W. P., Nelson, S. J., et al. (2001) · PubMed Central · Cited by 378
Bleeker, F. E., Lamba, S., Leenstra, S., Troost, D., Hulsebos, T. J. M., Vandertop, W. P., Frattini, M., Molinari, F., Knowles, M. A., Cerrato, A., et al. (2009) · Human Mutation · doi:10.1002/humu.20937 · Cited by 365
Cramér–Rao bounds: an evaluation tool for quantitation
Cavassila, S., Deval, S., Huegen, C., ORMONDT, D. V., & Graveron‐Demilly, D. (2001) · NMR in Biomedicine · doi:10.1002/nbm.701 · Cited by 333
Tedeschi, G., Lundbom, N. M. I., Raman, R., Bonavita, S., Duyn, J. H., Alger, J. R., & Chiro, G. D. (1997) · Journal of neurosurgery · doi:10.3171/jns.1997.87.4.0516 · Cited by 269
Chou, W., Hou, H., Chen, C., Tang, J., Yao, M., Tsay, W., Ko, B.-S., Wu, S., Huang, S., Hsu, S.-C., et al. (2010) · Blood · doi:10.1182/blood-2009-11-253070 · Cited by 208
IDH1 mutations in low-grade astrocytomas predict survival but not response to temozolomide
Dubbink, H. J., Taal, W., van Marion, R., Kros, J. M., van Heuvel, I., Bromberg, J. E. C., Zonnenberg, B. A., Zonnenberg, C. B. L., Postma, T. J., Gijtenbeek, J. M. M., et al. (2009) · Neurology · doi:10.1212/wnl.0b013e3181c34ace · Cited by 186
Hydroxyglutaric aciduria and malignant brain tumor: a case report and literature review
Aghili, M., Zahedi, F., & Rafiee, E. (2009) · Journal of Neuro-Oncology · doi:10.1007/s11060-008-9706-2 · Cited by 159
IDH1andIDH2Mutations in Gliomas
Carli, E. D., Wang, X.-W., & Puget, S. (2009) · New England Journal of Medicine · doi:10.1056/nejmc090593 · Cited by 134
Jin, G., Reitman, Z. J., Spasojevic, I., Batinic-Haberle, I., Yang, J., Schmidt-Kittler, O., Bigner, D. D., & Yan, H. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016812 · Cited by 112
van, Dubbink, Hj, Mariê, Brandes, Aa, TAPHOORN, M. J. B., Mj, Wesseling, P., Frenay, et al. (2010) · 中国神经肿瘤杂志 · Cited by 104
Molecular signatures classify astrocytic gliomas by IDH1 mutation status
Toedt, G., Barbus, S., Wolter, M., Felsberg, J., Tews, B., Blond, F., Sabel, M., Hofmann, S., Becker, N., Hartmann, C. J., et al. (2010) · International Journal of Cancer · doi:10.1002/ijc.25448 · Cited by 78
The principles of quantification applied to in vivo proton MR spectroscopy
Helms, G. (2008) · European Journal of Radiology · doi:10.1016/j.ejrad.2008.02.034 · Cited by 59
Proton magnetic resonance spectroscopy imaging in the study of human brain cancer.
Martínez‐Bisbal, M. C., & Celda, B. (2009) · PubMed · Cited by 35
Labussière, M., Wang, X.-W., Idbaïh, A., Ducray, F., & Sanson, M. (2010) · Future Oncology · doi:10.2217/fon.10.25 · Cited by 22
Research works printed but not linked: 1
- Ducray F, Marie Y, Sanson M (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360(21):2248 author reply 9 · DOI
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Boroughs, L. K., & DeBerardinis, R. J. (2015) · Nature Cell Biology · doi:10.1038/ncb3124 · Cited by 1,499
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Gamcsik, M. P., Kasibhatla, M. S., Teeter, S. D., & Colvin, O. M. (2012) · Biomarkers · doi:10.3109/1354750x.2012.715672 · Cited by 608
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Dunn, G. P., Rinne, M. L., Wykosky, J., Genovese, G., Quayle, S. N., Dunn, I. F., Agarwalla, P. K., Chheda, M. G., Campos, B., Wang, A., et al. (2012) · Genes & Development · doi:10.1101/gad.187922.112 · Cited by 573
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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