Actionable Targets Involving Fgf Receptors In Gliomas: Molecular Specificities, Spatial Distribution, Clinical Outcome And Radiological Phenotype

2005Background: to characterize clinical, molecular and radiological features of diffuse gliomas with FGFR3-TACC3 fusions or FGFR1 mutations, which are both actionable with new oral anti-FGFR inhibitors. Methods: We screened for FGFR3-TACC3 fusions 1112 gliomas (861 grade IV, 140 grade III and 111 grade II) by RT-PCR. We performed sequencing for hotspot FGFR1 mutations (N546 and K656) in 73 midline gliomas (8 grade II, 10 grade III, 54 grade IV, affecting cerebellum, spinal cord, brainstem, thalamus and diencephalon) and 479 hemispheric gliomas (170 grade IV, 151 grade III, 157 grade II). Results: We identified 50 gliomas (all IDH wild-type) with FGFR3-TACC3 fusion (45 grade IV, 2 grade III and 3 grade II). FGFR3-TACC3 fusion was mutually exclusive with EGFR amplification (p = 0.000) and co-occured with CDK4 and MDM2 amplifications (p = 0.011 and p = 0.005). FGFR3-TACC3 positive glioblastoma patients had a longer median overall survival (OS) (40.1 months versus 19.0; p = 0.006). Multivariate analysis show...