NDLI: Non-invasive quantification of 2-hydroxyglutarate in human gliomas with IDH1 and IDH2 mutations

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Non-invasive quantification of 2-hydroxyglutarate in human gliomas with IDH1 and IDH2 mutations

Content Provider	PubMed Central
Author	Emir, Uzay E. Larkin, Sarah J. Pennington, Nick De Natalie, Voets Plaha, Puneet Stacey, Richard Al-qahtani, Khalid Mccullagh, James Schofield, Christopher J. Clare, Stuart Jezzard, Peter Tom, Cadoux-hudson Ansorge, Olaf
Abstract	Mutations in the isocitrate dehydrogenase genes (IDH1/2) occur often in diffuse gliomas where they are associated with abnormal accumulation of the oncometabolite 2-hydroxyglutarate (2-HG). Monitoring 2-HG levels could provide prognostic information in this disease, but detection strategies that are non-invasive and sufficiently quantitative have yet to be developed. In this study, we address this need by presenting a proton magnetic resonance spectroscopy (1H MRS) acquisition scheme that uses an ultra-high magnetic field (≥7T) capable of noninvasively detecting 2-HG with quantitative measurements sufficient to differentiate mutant cytosolic IDH1 and mitochondrial IDH2 in human brain tumors. Untargeted metabolomics analysis of in vivo 1H MRS spectra discriminated between IDH mutant tumors and healthy tissue and separated IDH1 from IDH2 mutations. High-quality spectra enabled the quantification of neurochemical profiles consisting of at least eight metabolites, including 2-HG, glutamate, lactate, and glutathione in both tumor and healthy tissue voxels. Notably, IDH2 mutation produced more 2-HG than IDH1 mutation, consistent with previous findings in cell culture. By offering enhanced sensitivity and specificity, this scheme can quantitatively detect 2-HG and associated metabolites that may accumulate during tumor progression, with implications to better monitor patient responses to therapy.
Related Links	http://dx.doi.org/10.1158/0008-5472.CAN-15-0934
Ending Page	49
Page Count	7
Starting Page	43
File Format	PDF
ISSN	15387445
e-ISSN	15387445
Journal	Cancer research
Issue Number	1
Volume Number	76
Language	English
Publisher Date	2016-01-01
Access Restriction	Open
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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