A Noninvasive Comparison Study between Human Gliomas with IDH1 and IDH2 Mutations by MR Spectroscopy

Shen, Xin; Voets, Natalie L.; Larkin, Sarah J.; de Pennington, Nick; Plaha, Puneet; Stacey, Richard; McCullagh, James S. O.; Schofield, Christopher J.; Clare, Stuart; Jezzard, Peter; Cadoux-Hudson, Tom; Ansorge, Olaf; Emir, Uzay E.

doi:10.3390/metabo9020035

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A Noninvasive Comparison Study between Human Gliomas with IDH1 and IDH2 Mutations by MR Spectroscopy

^1,†,

^2,†,

^3,4,

⁴,

⁴,

James S. O. McCullagh

⁵,

Christopher J. Schofield

⁵

²,

²,

⁴,

³ and

^1,2,6,*

Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA

Wellcome Centre for Integrative Neuroimaging, FMRIB Division, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK

Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK

⁴

Department of Neurosurgery, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford OX3 9DU, UK

⁵

Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford OX1 3TA, UK

⁶

School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Metabolites 2019, 9(2), 35; https://doi.org/10.3390/metabo9020035

Received: 11 December 2018 / Revised: 5 February 2019 / Accepted: 15 February 2019 / Published: 20 February 2019

(This article belongs to the Special Issue Metabolomics in the Study of Disease)

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Abstract

The oncogenes that are expressed in gliomas reprogram particular pathways of glucose, amino acids, and fatty acid metabolism. Mutations in isocitrate dehydrogenase genes (IDH1/2) in diffuse gliomas are associated with abnormally high levels of 2-hydroxyglutarate (2-HG) levels. The aim of this study was to determine whether metabolic reprogramming associated with IDH mutant gliomas leads to additional ¹H MRS-detectable differences between IDH1 and IDH2 mutations, and to identify metabolites correlated with 2-HG. A total of 21 glioma patients (age= 37 ± 11, 13 males) were recruited for magnetic resonance spectroscopy (MRS) using semi-localization by adiabatic selective refocusing pulse sequence at an ultra-high-field (7T). For 20 patients, the tumor mutation subtype was confirmed by immunohistochemistry and DNA sequencing. LCModel analysis was applied for metabolite quantification. A two-sample t-test was used for metabolite comparisons between IDH1 (n = 15) and IDH2 (n = 5) mutant gliomas. The Pearson correlation coefficients between 2-HG and associated metabolites were calculated. A Bonferroni correction was applied for multiple comparison. IDH2 mutant gliomas have a higher level of 2-HG/tCho (total choline=phosphocholine+glycerylphosphorylcholine) (2.48 ± 1.01vs.0.72 ± 0.38, P_c < 0.001) and myo-Inositol/tCho (2.70 ± 0.90 vs. 1.46 ± 0.51, P_c = 0.011) compared to IDH1 mutation gliomas. Associated metabolites, myo-Inositol and glucose+taurine were correlated with 2-HG levels. These results show the improved characterization of the metabolic pathways in IDH1 and IDH2 gliomas for precision medicine. View Full-Text

Keywords: glioma; isocitrate dehydrogenase; MR spectroscopy; metabolism; neurochemical profile

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Shen, X.; Voets, N.L.; Larkin, S.J.; de Pennington, N.; Plaha, P.; Stacey, R.; McCullagh, J.S.O.; Schofield, C.J.; Clare, S.; Jezzard, P.; Cadoux-Hudson, T.; Ansorge, O.; Emir, U.E. A Noninvasive Comparison Study between Human Gliomas with IDH1 and IDH2 Mutations by MR Spectroscopy. Metabolites 2019, 9, 35. https://doi.org/10.3390/metabo9020035

AMA Style

Shen X, Voets NL, Larkin SJ, de Pennington N, Plaha P, Stacey R, McCullagh JSO, Schofield CJ, Clare S, Jezzard P, Cadoux-Hudson T, Ansorge O, Emir UE. A Noninvasive Comparison Study between Human Gliomas with IDH1 and IDH2 Mutations by MR Spectroscopy. Metabolites. 2019; 9(2):35. https://doi.org/10.3390/metabo9020035

Chicago/Turabian Style

Shen, Xin, Natalie L. Voets, Sarah J. Larkin, Nick de Pennington, Puneet Plaha, Richard Stacey, James S.O. McCullagh, Christopher J. Schofield, Stuart Clare, Peter Jezzard, Tom Cadoux-Hudson, Olaf Ansorge, and Uzay E. Emir. 2019. "A Noninvasive Comparison Study between Human Gliomas with IDH1 and IDH2 Mutations by MR Spectroscopy" Metabolites 9, no. 2: 35. https://doi.org/10.3390/metabo9020035

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A Noninvasive Comparison Study between Human Gliomas with IDH1 and IDH2 Mutations by MR Spectroscopy

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