BIOM-17. WHOLE GAIN OF CHROMOSOME 19, NOT CO-GAIN OF CHROMOSOMES 19 AND 20, IS A FAVORABLE PROGNOSTIC BIOMARKER IN IDH-WILDTYPE GLIOBLASTOMA

Abstract

Abstract BACKGROUND IDH-wildtype glioblastoma carries an abysmal prognosis, but long-term survivors exist. Previous studies have suggested that co-gain of chromosomes 19 and 20 (+19/+20) is a favorable prognostic marker. We sought to validate this claim and investigate whether gain of chromosome 19 (+19) is a superior prognostic indicator. METHODS We collected somatic copy number alteration data for primary glioblastoma tumors from TCGA (N = 356) and paired primary (N = 169) and recurrent (N = 167) glioblastoma tumors from GLASS. We assessed the frequency of these events and conducted survival analyses with univariate and multivariate Cox proportional hazard models to examine the association between +19/+20 and +19 and patient outcomes. RESULTS Among primary glioblastomas, the frequency of +19/+20 (20.8% vs. 23.7%) and +19 (34.6% vs. 36.7%) did not differ between TCGA and GLASS. However, the presence of +19/+20 was significantly reduced in GLASS recurrent tumors compared to primary tumors (14.3%, p = 0.04), while +19 without +19/+20 was unchanged (13.8%), indicating that +19/+20 is selected against in recurrent glioblastoma. Tumors harboring +19/+20 did not exhibit improved overall survival (OS) or progression-free survival (PFS) in TCGA (p = 0.21 and p = 0.14, respectively), nor did they demonstrate improved OS in GLASS (p = 0.32). Conversely, tumors with +19 showed significantly better OS and PFS in TCGA (HR = 1.4, p< 0.01; HR = 1.5, p< 0.01, respectively) and improved OS in GLASS (HR = 1.6, p< 0.01). In multivariate survival analyses, +19 remained a prognostic factor independent of +19/+20, patient sex, age, MGMT promoter methylation status, and KPS in TCGA (p< 0.05) and +19/+20 and age in GLASS (p = 0.01). CONCLUSION Although previous studies have suggested that +19/+20 is a positive prognostic biomarker in glioblastoma, our findings indicate that this assertion should be reevaluated. Our results demonstrate that +19 is associated with favorable outcomes in the TCGA and GLASS datasets, whereas +19/+20, while possibly selected against in recurrent glioblastomas, is not.