Mutant IDH1 gliomas downregulate phosphocholine and phosphoethanolamine synthesis in a 2-hydroxyglutarate-dependent manner.

ABSTRACT:

Background

Magnetic resonance spectroscopy (MRS) studies have identified elevated levels of the phospholipid precursor phosphocholine (PC) and phosphoethanolamine (PE) as metabolic hallmarks of cancer. Unusually, however, PC and PE levels are reduced in mutant isocitrate dehydrogenase 1 (IDHmut) gliomas that produce the oncometabolite 2-hydroxyglutarate (2-HG) relative to wild-type IDH1 (IDHwt) gliomas. The goal of this study was to determine the molecular mechanism underlying this unusual metabolic reprogramming in IDHmut gliomas.

Methods

Steady-state PC and PE were quantified using ³¹P-MRS. To quantify de novo PC and PE synthesis, we used ¹³C-MRS and measured flux to ¹³C-PC and ¹³C-PE in cells incubated with [1,2-¹³C]-

SUBMITTER: Viswanath P 

PROVIDER: S-EPMC5881177 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature