Altered metabolic landscape in IDH-mutant gliomas affects phospholipid, energy, and oxidative stress pathways.

ABSTRACT: Heterozygous mutations in NADP-dependent isocitrate dehydrogenases (IDH) define the large majority of diffuse gliomas and are associated with hypermethylation of DNA and chromatin. The metabolic dysregulations imposed by these mutations, whether dependent or not on the oncometabolite D-2-hydroxyglutarate (D2HG), are less well understood. Here, we applied mass spectrometry imaging on intracranial patient-derived xenografts of IDH-mutant versus IDH wild-type glioma to profile the distribution of metabolites at high anatomical resolution in situ This approach was complemented by in vivo tracing of labeled nutrients followed by liquid chromatography-mass spectrometry (LC-MS) analysis. Selected metabolites were verified on clinical specimen. Our data identify remarkable difference

SUBMITTER: Fack F 

PROVIDER: S-EPMC5709746 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature