Purine salvage promotes treatment resistance in H3K27M-mutant diffuse midline glioma.

ABSTRACT:

Background

Diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPGs), are a fatal form of brain cancer. These tumors often carry a driver mutation on histone H3 converting lysine 27 to methionine (H3K27M). DMG-H3K27M are characterized by altered metabolism and resistance to standard of care radiation (RT) but how the H3K27M mediates the metabolic response to radiation and consequent treatment resistance is uncertain.

Methods

We performed metabolomics on irradiated and untreated H3K27M isogenic DMG cell lines and observed an H3K27M-specific enrichment for purine synthesis pathways. We profiled the expression of purine synthesis enzymes in publicly available patient data and our models, quantified purine synthesis using stable isotope tracing, and char

SUBMITTER: Peterson ER 

PROVIDER: S-EPMC11003124 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature