Multi-scale signaling and tumor evolution in high-grade gliomas.
Publication/Presentation Date
7-8-2024
Abstract
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.
Volume
42
Issue
7
First Page
1217
Last Page
1238
ISSN
1878-3686
Published In/Presented At
Liu, J., Cao, S., Imbach, K. J., Gritsenko, M. A., Lih, T. M., Kyle, J. E., Yaron-Barir, T. M., Binder, Z. A., Li, Y., Strunilin, I., Wang, Y. T., Tsai, C. F., Ma, W., Chen, L., Clark, N. M., Shinkle, A., Naser Al Deen, N., Caravan, W., Houston, A., Simin, F. A., … Clinical Proteomic Tumor Analysis Consortium (2024). Multi-scale signaling and tumor evolution in high-grade gliomas. Cancer cell, 42(7), 1217–1238.e19. https://doi.org/10.1016/j.ccell.2024.06.004
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
38981438
Department(s)
Administration and Leadership
Document Type
Article