Publication Date
4-12-2021
Journal
Cancer Cell
DOI
10.1016/j.ccell.2021.01.006
PMID
33577785
PMCID
PMC8044053
PubMedCentral® Posted Date
4-12-2022
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Keywords
Brain Neoplasms, Computational Biology, Glioblastoma, Humans, Metabolomics, Mutation, Phospholipase C gamma, Phosphorylation, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Proteogenomics, Proteomics
Abstract
Glioblastoma (GBM) is the most aggressive nervous system cancer. Understanding its molecular pathogenesis is crucial to improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification and metabolomic data on 99 treatment-naive GBMs provides insights to GBM biology. We identify key phosphorylation events (e.g., phosphorylated PTPN11 and PLCG1) as potential switches mediating oncogenic pathway activation, as well as potential targets for EGFR-, TP53-, and RB1-altered tumors. Immune subtypes with distinct immune cell types are discovered using bulk omics methodologies, validated by snRNA-seq, and correlated with specific expression and histone acetylation patterns. Histone H2B acetylation in classical-like and immune-low GBM is driven largely by BRDs, CREBBP, and EP300. Integrated metabolomic and proteomic data identify specific lipid distributions across subtypes and distinct global metabolic changes in IDH-mutated tumors. This work highlights biological relationships that could contribute to stratification of GBM patients for more effective treatment.
Graphical Abstract
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Biochemistry, Biophysics, and Structural Biology Commons, Biology Commons, Biomedical Informatics Commons, Medical Sciences Commons, Oncology Commons
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