DIPG-30. HIF2 OVEREXPRESSION DICTATES AGGRESSIVENESS ADDITIONALLY TO TP53 MUTATIONS IN H3.3K27M PEDIATRIC HIGH-GRADE GLIOMAS THROUGH RAS-MAPK AND WNT/BCATENIN PATHWAYS

Abstract Diffuse midline (DMG) and brainstem (DIPG) high-grade gliomas (HGG) bearing H3.3K27M driver mutation are aggressive uncurable brain tumors. We evidenced by the past HIF-2a its transcriptional gene, EPAS1, as a marker of resistance when targeting mTor/HIF-1a pathway. To understand HIF-2α potential role in chronically active hypoxic environment DIPG/DMG, we investigate status cohort pediatric HGGs comprising notably mutant tumors their paired vitro derived models. Using concomitantly low-input chromatin immunoprecipitation sequencing method CUT&RUN, RNAsequencing metabolomics, profiled landscape promoters pathways regulated HGGs, where TP53 mutations associated. Elucidation downstream genes reveal statistically significant linked to DIPGs (e.g., mTor canonical Wnt pathways) DMGs (glutamatergic synapse non-canoncial signaling). Finally, was new therapeutic target opening path for use irradiation.