CDKN2A deletion remodels lipid metabolism to prime glioblastoma for ferroptosis

Malignant tumors exhibit heterogeneous metabolic reprogramming, hindering the identification of translatable vulnerabilities for metabolism-targeted therapy. How molecular alterations in tumors promote metabolic diversity and distinct targetable dependencies remains poorly defined. Here we create a resource consisting of lipidomic, transcriptomic, and genomic data from 156 molecularly diverse glioblastoma (GBM) tumors and derivative models. Through integrated analysis of the GBM lipidome with molecular datasets, we identify CDKN2A deletion remodels the GBM lipidome, notably redistributing oxidizable polyunsaturated fatty acids into distinct lipid compartments. Consequently, CDKN2A-deleted GBMs display higher…

• UD
  U.S. Department of Defense

  Award: W81XWH
• NI
  National Institutes of Health

  Awards: P50CA211015, W81XWH, R01CA227089, P01HL146358, R01NS121319