Intratumoral heterogeneity and genetic testing utilization in glioblastoma patients: A retrospective study at the University of Vermont Medical Center.

Abstract

e14091 Background: Glioblastoma (GBM) is a primary malignant tumor characterized by intratumoral heterogeneity. Key biomarkers including isocitrate dehydrogenase (IDH) mutation status and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, as well as expanded molecular profiling, are critical to diagnosis, prognosis, and therapeutic decision-making. This study aims to investigate the number of patients who received standard and expanded genetic testing at the University of Vermont Medical Center (UVMMC) and explore differences in testing by gender and geographic residence. The study sought to identify the frequency of key mutations involving oncogenic signaling pathways, tumor suppressor function, and cell cycle regulation. Methods: A retrospective review was undertaken of electronic health records of 90 patients with GBM from 2021 to 2023 followed at UVMMC. We assessed all patients offered basic genetic testing, specifically IDH and MGMT promoter methylation, and the subset of patients who proceeded to receive expanded genetic testing. Demographic factors, including gender and geographic residence by zip code, were also assessed, with a focus on frequency of testing between patients residing in Chittenden County versus rural and New York-bordering regions. Results: Amongst 90 patients diagnosed with GBM at UVMMC, 97% of patients were offered basic genetic testing. Approximately 2% of patients demonstrated IDH mutations, consistent with predominantly IDH-wildtype GBM, while MGMT promoter methylation was observed in 39% of patients. 45% of patients proceeded to receive expanded testing, revealing TERT promoter mutations (56%) and CDKN2A/B loss (46%) as the most prevalent alterations. EGFR (39%), PTEN (33%), and TP53 alterations (33%) were also commonly identified. Less frequent mutations included MET (18%), FGFR (15%), PDGFRA/KIT/KDR (13%), NF1 (13%), and major chromosomal mutations (13%). Demographic analysis demonstrated males and females underwent standard and expanded testing at comparable rates. While basic genetic testing was performed nearly universally across urban (100%) and rural (96%) patients, those in urban settings received additional genetic testing at a significantly higher rate (58%) compared to rural patients (38%). Conclusions: Comprehensive molecular profiling in patients with GBM at UVMMC identified TERT promoter mutations and CDKN2A/B loss amongst the most common alterations. Testing rates were similar between males and females, while patients in urban areas were more likely to undergo expanded testing, likely driven by a difference in socioeconomic status and proximity to a medical center. Our findings highlight diverse genetic mutations and demographic factors influencing testing, providing opportunity to guide targeted therapies and optimize access to precision oncology.