Abstract
This prospective population-based study on a group of 132 resected IDH-wildtype (IDH-wt) glioblastoma (GBM) patients assesses the prognostic and predictive value of selected genetic biomarkers and clinical factors for GBM as well as the dependence of these values on the applied therapeutic modalities. The patients were treated in our hospital between June 2006 and June 2015. Clinical data and tumor samples were analyzed to determine the frequencies of TP53, MDM2, EGFR, RB1, BCR, and CCND1 gene aberrations and the duplication/deletion statuses of the 9p21.3, 1p36.3, 19q13.32, and 10p11.1 chromosome regions. Cut-off values distinguishing low (LCN) and high (HCN) copy number status for each marker were defined. Additionally, MGMT promoter methylation and IDH1/2 mutation status were investigated retrospectively. Young age, female gender, Karnofsky scores (KS) above 80, chemoradiotherapy, TP53 HCN, and CCND1 HCN were identified as positive prognostic factors, and smoking was identified as a negative prognostic factor. Cox proportional regression models of the chemoradiotherapy patient group revealed TP53 HCN and CCND1 HCN to be positive prognostic factors for both progression-free survival and overall survival. These results confirmed the influence of key clinical factors (age, KS, adjuvant oncotherapy, and smoking) on survival in GBM IDH-wt patients and demonstrated the prognostic and/or predictive importance of CCND1, MDM2, and 22q12.2 aberrations.
Highlights
Glioblastoma (GBM) is a highly invasive tumor type that is not amenable to complete resection [1,2,3]
GBM with wt isocitrate dehydrogenase (IDH) is characterized by tumor protein p53 (TP53) mutations, phosphatase tensin homolog (PTEN) mutations and/or complete loss of chromosome 10, homozygous deletion of cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/CDKN2B), mutation or overexpression of epidermal growth factor receptor (EGFR), and/or gain of the 7p chromosome arm, platelet-derived growth factor receptor 1 (PDFGRA1) mutations, neurofibromin 1 (NF1) mutations, E3 ubiquitin-protein ligase (MDM2) amplification, and methylguanine-DNA methyltransferase (MGMT) promoter methylation [10]
We studied a cohort of IDH wt glioblastoma patients whose IDH status was determined in accordance with the WHO recommendations of 2016 [11,12]
Summary
Glioblastoma (GBM) is a highly invasive tumor type that is not amenable to complete resection [1,2,3]. Clinical factors including young age, good performance status, gross total resection, and adjuvant treatment have been linked to superior prognosis among unselected GBM patients [6,7,8,9]. GBM with wt IDH is characterized by tumor protein p53 (TP53) mutations, phosphatase tensin homolog (PTEN) mutations and/or complete loss of chromosome 10, homozygous deletion of cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/CDKN2B), mutation or overexpression of epidermal growth factor receptor (EGFR), and/or gain of the 7p chromosome arm, platelet-derived growth factor receptor 1 (PDFGRA1) mutations, neurofibromin 1 (NF1) mutations, E3 ubiquitin-protein ligase (MDM2) amplification, and methylguanine-DNA methyltransferase (MGMT) promoter methylation [10]
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