Multi-scale signaling and tumor evolution in high-grade gliomas

Multi-scale signaling and tumor evolution in high-grade gliomas CPTAC Charlotte Sack… Fri, 03/20/2026 - 14:28 CPTAC Cell . Volume 42 , Issue 7: p. 1217-1238.e19, 8 Jul 2024 10.1016/j.ccell.2024.06.004 Although genomic anomalies in glioblastoma (GBM) have been well studied for over a decade, its 5-year survival rate remains lower than 5%. We seek to expand the molecular landscape of high-grade glioma, composed of IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma, by integrating proteomic, metabolomic, lipidomic, and post-translational modifications (PTMs) with genomic and transcriptomic measurements to uncover multi-scale regulatory interactions governing tumor development and evolution. Applying 14 proteogenomic and metabolomic platforms to 228 tumors (212 GBM and 16 grade 4 IDH-mutant astrocytoma), including 28 at recurrence, plus 18 normal brain samples and 14 brain metastases as comparators, reveals heterogeneous upstream alterations converging on common downstream events at the proteomic and metabolomic levels and changes in protein-protein interactions and glycosylation site occupancy at recurrence. Recurrent genetic alterations and phosphorylation events on PTPN11 map to important regulatory domains in three dimensions, suggesting a central role for PTPN11 signaling across high-grade gliomas. Instructions for Data Download Open Access Data Download the appropriate manifest file from the publication page Use the manifest file to download data using the GDC Data Transfer Tool (DTT) or the GDC API GDC DTT ( Download , User’s Guide ) GDC API ( User’s Guide ) Controlled Access Data Download the appropriate manifest file from the publication page Download a token from the GDC Data Portal GDC Data Portal ( Launch , User’s Guide ) Use the manifest file and token to download data using the GDC DTT or the GDC API GDC DTT ( Download , User’s Guide ) GDC API ( User’s Guide ) For assistance, please contact the GDC Help Desk: support@nci-gdc.datacommons.io .