TMIC-19. NEURODEVELOPMENTAL SUBTYPES SHAPE LIPID METABOLIC REPROGRAMMING IN GLIOMAS

Abstract Gliomas have been classified into molecular (proneural, classical, mesenchymal) and neurodevelopmental (astrocyte, mesenchymal, neural progenitor cell (NPC), oligodendrocyte (OPC)) subtypes describing inter- intra-tumoral heterogeneity; however, the functional outcomes therapeutic implications of these has yet to be fully described. Metabolic reprogramming is a hallmark cancer, malignant cells, including gliomas, acquire metabolic adaptations in response multitude intrinsic (oncogenotype, mutations) extrinsic (tumor microenvironment) factors fuel neoplastic progression. Altered metabolism glioma particular interest given extensive heterogeneity tumors, while also developing brain microenvironment, tissue known for its unique milieu. It unknown whether influence gliomas. Preliminary comprehensive lipidomic transcriptomic analysis over 200 patient-derived samples revealed that distinct lipid signatures were linked subtypes. Specifically, proneural-like gliomas (OPC, NPC, Neuron) had profile enriched ether lipids. Conversely, mesenchymal-like (radial glia, MES.progenitor, vascular) triacylglycerides (TAGs). Intriguingly, differences programs between associated with environmental dependencies; contrast more mesenchymal like which could grow irrespective tumor microenvironment (brain or vitro culture), required features accumulate complex fatty acids grow. Collectively, data emphasize within reveal subset lack plasticity acid biosynthetic programs, indicating potential brain-microenvironment specific dependency transcriptional identity may targeted therapy.