Glioblastoma Project

Glioblastoma (GBM) is the most common malignant brain tumor that accounts for 15% of all primary brain tumors and 45% of primary malignant brain tumors. It has a poor prognosis of only 5% survival at 5 years with a median survival of 14-15 months. GBM tumor samples were analyzed by The Cancer Genome Atlas (TCGA) project revealing that the most frequently mutated genes include TP53, PTEN, EGFR, NF1, PIK3R1, RB1, and PIK3CA. The DNA copy-number alteration showed the most frequent deletion events on chromosomes 9 (CDKN2A/B), 13 (RB1), 1 (CDKN2C) and 10 (PTEN), and most frequent amplifications on chromosomes 7 (EGFR/MET/CDK6), 12 (CDK4 and MDM2), and 4 (PDGFRA). These mutations and copy number alterations define the core biological pathways that are deregulated in GBM including the RTK/RAS/PI3K, p53, and RB signaling pathways. The TCGA analysis also identified different GBM molecular subtypes: proneural, neural, classical and mesenchymal. Proneural subtypes involve abnormalities in PDGFRA and IDH1. The neural subtype displays a similar genetic profile to that found in normal brain tissue, with expression of neuronal markers such as NEFL, GABRA1, SYT1 and SLC12A5. The classical subtype has the most common genomic aberrations, with 93% of GBM samples harboring chromosome 7 amplification and chromosome 10 deletion accompanied with EGFR amplification and homozygous deletion of the CDKN2A-p16 Ink4a/ARF locus, as well as lack of TP53 mutations. The mesenchymal subgroup is characterized by abnormalities in NF1, mutation/deletion, with high expression of mesenchymal (CHI3L1 and MET) and astrocytic (CD44 and MERTK) markers. This classification system is further refined based on characterization of DNA methylation patterns, as proneural GBM into glioma-CpG island methylator phenotype (G- CIMP) positive and G-CIMP negative GBM subsets, which corresponds strongly with IDH1 mutations.

BioGRID curators identified critical genes involved in Glioblastoma and manually curated their corresponding molecular interactions from the literature. The different proteins on the GBM list were further classified into 13 functional categories and three subcategories: oncogenes, tumor suppressors and cancer drivers based on assignments in CancerMine. This Glioblastoma project page allows users to explore the GBM gene list, as well as any corresponding protein interactions, post translation modifications (PTMs) and chemical interactions.

If you wish to help contribute to this project or to submit a dataset to BioGRID, please contact us at biogridadmin@gmail.com. All Glioblastoma project curated data records are freely available for download from links within this project.

H. sapiens

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Curated Protein List