Next Article in Journal
Function, Detection and Alteration of Acylcarnitine Metabolism in Hepatocellular Carcinoma
Next Article in Special Issue
Propolis Exerts an Anti-Inflammatory Effect on PMA-Differentiated THP-1 Cells via Inhibition of Purine Nucleoside Phosphorylase
Previous Article in Journal
Metabolomics Approaches for the Diagnosis and Understanding of Kidney Diseases
Article Menu
Issue 2 (February) cover image

Export Article

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

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

1
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA
2
Wellcome Centre for Integrative Neuroimaging, FMRIB Division, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK
3
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.
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)
  |  
PDF [2644 KB, uploaded 20 February 2019]
  |  

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, Pc < 0.001) and myo-Inositol/tCho (2.70 ± 0.90 vs. 1.46 ± 0.51, Pc = 0.011) compared to IDH1 mutation gliomas. Associated metabolites, myo-Inositol and glucose+taurine were correlated with 2-HG levels. These results show 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 glioma; isocitrate dehydrogenase; MR spectroscopy; metabolism; neurochemical profile
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Metabolites EISSN 2218-1989 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top