Gene-09. Comprehensive Genetic Alteration Profiling in Primary and Recurrent Glioblastoma
Year: 2017
Type: conference-abstract
Abstract: Glioblastoma (GBM) is known to be heterogeneous, but a knowledge gap exists regarding its genetic alterations and their influence on evolution, resistance, and therapeutic response. The FoundationOne® comprehensive genomic profile was utilized to analyze ten patients’ matched primary and recurrent GBM. The profile looks for mutations, indels, copy number alterations (CNAs), and rearrangements in 315 genes and 28 introns via next-generation sequencing (NGS). These alterations were further characterized as mutations with known/likely cancer-promoting function or variants of unknown significance. Patient clinical information was reviewed for associations with genetic alterations. Identified mutations in our cohort were compared with known mutations in GBM from the Catalogue Of Somatic Mutations in Cancer (COSMIC). All tumors demonstrated genetic alterations between the primary and recurrence including one which was resected without intervening therapy. This suggests that time and/or therapeutic intervention contribute to genetic alterations in GBM. Although there were mutations common to both the primary and recurrence, the percent reads between the two often varied substantially suggesting clonal expansion and contraction. For example, EGFR mutations were significantly expanded in three patients, and CNAs were increased in two patients at recurrence. Four genes were commonly altered in primary and recurrent GBM and were more prevalent in our cohort than in the COSMIC database: CDKN2A (86% vs 53%) and CDKN2B (86% vs 54%) deletion, EGFR activating mutation (52% vs 10%) or amplification (81% vs 45%), and TERT mutation (95% vs 51%). Lastly, PI3K pathway activating mutations were also commonly seen in our cohort (67%). NGS revealed that GBM changed over time and with treatment. Mutations in TERT, CDKN2A/CDKN2B, EGFR, and PI3K pathway were commonly observed in both primary and recurrent GBM revealing their prognostic and therapeutic potential. This may have important implications for individualized therapies and may be evaluated with a larger cohort.
Source: Neuro-Oncology
Institution: University of Nebraska Medical Center
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2767478981