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Detection of 2-Hydroxyglutarate in IDH-Mutated Glioma Patients by In Vivo Spectral-Editing and 2D Correlation Magnetic Resonance Spectroscopy.
MedLine Citation:
PMID:  22238332     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Mutations in the gene isocitrate dehydrogenase 1 (IDH1) are present in up to 86% of grade II and III gliomas and secondary glioblastoma. Arginine 132 (R132) mutations in the enzyme IDH1 result in excess production of the metabolite 2-hydroxyglutarate (2HG), which could be used as a biomarker for this subset of gliomas. Here, we use optimized in vivo spectral-editing and two-dimensional (2D) correlation magnetic resonance spectroscopy (MRS) methods to unambiguously detect 2HG noninvasively in glioma patients with IDH1 mutations. By comparison, fitting of conventional 1D MR spectra can provide false-positive readouts owing to spectral overlap of 2HG and chemically similar brain metabolites, such as glutamate and glutamine. 2HG was also detected using 2D high-resolution magic angle spinning MRS performed ex vivo on a separate set of glioma biopsy samples. 2HG detection by in vivo or ex vivo MRS enabled detailed molecular characterization of a clinically important subset of human gliomas. This has implications for diagnosis as well as monitoring of treatments targeting mutated IDH1.
Authors:
Ovidiu C Andronesi; Grace S Kim; Elizabeth Gerstner; Tracy Batchelor; Aria A Tzika; Valeria R Fantin; Matthew G Vander Heiden; A Gregory Sorensen
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Science translational medicine     Volume:  4     ISSN:  1946-6242     ISO Abbreviation:  Sci Transl Med     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101505086     Medline TA:  Sci Transl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  116ra4     Citation Subset:  IM    
Affiliation:
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
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