Comparative proteogenomic characterization of glioblastoma
- PMID: 31290679
- PMCID: PMC6713026
- DOI: 10.2217/cns-2019-0003
Comparative proteogenomic characterization of glioblastoma
Abstract
Aim: Glioblastoma multiforme (GBM) carries a dismal prognosis. Integrated proteogenomic analysis was performed to understand GBM pathophysiology. Patients & methods: 17 patient samples were analyzed for driver mutations, oncogenes, major pathway alterations and molecular changes at gene and protein level. Clinical, treatment and survival data were collected. Results: Significantly mutated genes included TP53, EGFR, PIK3R1, PTEN, NF1, RET and STAG2. EGFR mutations noted included EGFRvIII-expression, EGFR-L816Q missense mutation-exon 21 and EGFR fusion (FGFR3-TACC3). TP53 mutations were noticed in COSMIC hot-spot driver gene and accompany IDH1 and ATRX mutations suggesting low- to high-grade glioma transformation. Proteomics showed higher (53%) EGFR expression than genomic expression (23%). MGMT methylation was present in two-thirds of cases. Conclusion: This study identifies a distinct biological process that may characterize each GBM differently. Proteogenomic data identify potential therapeutic targets of GBM.
Keywords: genomics; glioblastoma; proteomics; survival; temozolomide chemotherapy.
Conflict of interest statement
The author S Raza is a member of advisory board and speaker bureau for Amgen, Celgene, Takeda, Novartis and Janssen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
References
-
- Stupp R, Mason WP, van den Bent MJ. et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 352(10), 987–996 (2005). - PubMed
-
- Mjelle R, Hegre SA, Aas PA. et al. Cell cycle regulation of human DNA repair and chromatin remodeling genes. DNA Repair (Amst.) 30, 53–67 (2015). - PubMed
-
- Esteller M, Garcia-FOncillas J, Andion E. et al. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N. Engl. J. Med. 343(19), 1350–1354 (2000). - PubMed
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