MPTH-02. EXTRACELLULAR EGFR289 ACTIVATING MUTATIONS CONFER POORER SURVIVAL AND SUGGEST ENHANCED MOTILITY IN PRIMARY GBMs

Abstract

Glioblastoma (GBM) is the most common adult, malignant, primary brain tumor. Approximately 60% of GBMs harbor an EGFR alteration. The most common alteration is amplification, followed by the EGFR variant III mutation (EGFRvIII), and then various point mutations. We examined a retrospective cohort of GBM patients operated on at the Hospital of the University of Pennsylvania for point mutations in EGFR and assessed their correlation with clinical outcomes and advanced radiographic imaging. Here we report a negative survival correlation with a substitution of alanine at residue 289 (A289) and advanced magnetic resonance imaging (MRI) features associated with the presence of an A289 point mutation. These multi-parametric features suggested a radiographic signature of more aggressively infiltrating and proliferating tumors when compared to imaging from patients without an A289 point mutation. Additionally, several features were distinct from a previously developed EGFRvIII advanced MRI signature. Taken together, these data reveal that the A289 mutation may identify a subset of GBMs with poor survival and a specific advanced MRI signature suggestive of enhanced motility and invasion.