MTAP Loss Promotes Stemness in Glioblastoma and Confers Unique Susceptibility to Purine Starvation.

ABSTRACT: Homozygous deletion of methylthioadenosine phosphorylase (MTAP) is one of the most frequent genetic alterations in glioblastoma (GBM), but its pathologic consequences remain unclear. In this study, we report that loss of MTAP results in profound epigenetic reprogramming characterized by hypomethylation of PROM1/CD133-associated stem cell regulatory pathways. MTAP deficiency promotes glioma stem-like cell (GSC) formation with increased expression of PROM1/CD133 and enhanced tumorigenicity of GBM cells and is associated with poor prognosis in patients with GBM. As a combined consequence of purine production deficiency in MTAP-null GBM and the critical dependence of GSCs on purines, the enriched subset of CD133⁺ cells in MTAP-null GBM can be effec

SUBMITTER: Hansen LJ 

PROVIDER: S-EPMC6810595 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature