Preprint Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 11 December 2018 / Approved: 13 December 2018 / Online: 13 December 2018 (13:52:56 CET)

How to cite: Shen, X.; Voets, N.; Larkin, S.; de Pennington, N.; Stacey, R.; Plaha, P.; McCullagh, J.; Schofield, C.J.; Clare, S.; Jezzard, P.; Cadoux-Hudson, T.; Ansorge, O.; Emir, U. A Noninvasive Comparison Study between Human Gliomas with IDH1 and IDH2 Mutations by MR Spectroscopy. Preprints 2018, 2018120168 (doi: 10.20944/preprints201812.0168.v1). Shen, X.; Voets, N.; Larkin, S.; de Pennington, N.; Stacey, R.; Plaha, P.; McCullagh, J.; Schofield, C.J.; Clare, S.; Jezzard, P.; Cadoux-Hudson, T.; Ansorge, O.; Emir, U. A Noninvasive Comparison Study between Human Gliomas with IDH1 and IDH2 Mutations by MR Spectroscopy. Preprints 2018, 2018120168 (doi: 10.20944/preprints201812.0168.v1).

Abstract

The oncogenes that are expressed in gliomas reprogram particular pathways of glucose, amino acid, 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= 3711, 13 males) were recruited for MRS using a Semi-localization by adiabatic selective refocusing pulse sequence at ultra-high-field (7T). Tumour 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) (2.481.01vs.0.720.38, Pc<0.001) and myo-Inositol/tCho (2.700.90vs.1.460.51, Pc=0.011) compared to IDH1 mutation gliomas. Associated metabolites, myo-Inositol and glucose+taurine were correlated with 2-HG levels. These results show improved characterization of the metabolic pathways in IDH1 and IDH2 gliomas for precision medicine.

Subject Areas

glioma, isocitrate dehydrogenase, MR spectroscopy, metabolism, neurochemical profile

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