Document Detail


Magnetic Resonance of 2-Hydroxyglutarate in IDH1-Mutated Low-Grade Gliomas.
MedLine Citation:
PMID:  22238333     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Recent studies have indicated that a significant survival advantage is conferred to patients with gliomas whose lesions harbor mutations in the genes isocitrate dehydrogenase 1 and 2 (IDH1/2). IDH1/2 mutations result in aberrant enzymatic production of the potential oncometabolite d-2-hydroxyglutarate (2HG). Here, we report on the ex vivo detection of 2HG in IDH1-mutated tissue samples from patients with recurrent low-grade gliomas using the nuclear magnetic resonance technique of proton high-resolution magic angle spinning spectroscopy. Relative 2HG levels from pathologically confirmed mutant IDH1 tissues correlated with levels of other ex vivo metabolites and histopathology parameters associated with increases in mitotic activity, relative tumor content, and cellularity. Ex vivo spectroscopic measurements of choline-containing species and in vivo magnetic resonance measurements of diffusion parameters were also correlated with 2HG levels. These data provide extensive characterization of mutant IDH1 lesions while confirming the potential diagnostic value of 2HG as a surrogate marker of patient survival. Such information may augment the ability of clinicians to monitor therapeutic response and provide criteria for stratifying patients to specific treatment regimens.
Authors:
Adam Elkhaled; Llewellyn E Jalbert; Joanna J Phillips; Hikari A I Yoshihara; Rupa Parvataneni; Radhika Srinivasan; Gabriela Bourne; Mitchel S Berger; Susan M Chang; Soonmee Cha; Sarah J Nelson
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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:  116ra5     Citation Subset:  IM    
Affiliation:
Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94158, USA.
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