FGFR1 gene aberrations and FGFR1 protein expression in squamous non-small cell lung cancer (Sq-NSCLC)

The FGFR1 amplification proved unreliable as the predictive biomarker for FGFR inhibitors (FGFRIs) in the treatment of Sq-NSCLC. It was suggested that other genomic aberrations within FGFR1 and other genes might affect response to FGFRIs. We aimed to comprehensively evaluate the set of genomic and proteomic markers linked to FGFRs and other genes associated with lung cancer. 19 (stage IIA–IIIB;G2-G3) out of Sq-NSCLC 204 tumors with known FGFR1 amplification (FISH) and protein expression (IHC) were analyzed for FGFR1 mRNA level with RT-PCR and NanoString, and for fusions, variants and expression of FGFRs, ALK, BRAF, EGFR, KRAS, MET, NRG1, NTRK1-3, RET and ROS1 using FusionPlex Lung (ArcherDx) NGS assay. FGFR1 mRNA expression assessed by RT-PCR correlated with NGS analysis (r=0.61,p=0.012) and Nanostring analysis (r=0.82,p=0.00002). Concurrent high FGFR1 expression, FGFR1 gene amplification and protein expression (p = 0.02) was observed in double positive (FISH-/IHC-) in contrast to double negative (FISH-/IHC-) tumors. Targeted NGS analysis revealed new gene fusion transcripts (n=7) in 11 samples (68.7%). Clinically relevant gene variants (KRAS, EGFR, ROS1) were identified in 3 tumors (19%). Simultaneous analysis of FGFR and other genes aberrations may contribute to better understand of the Sq-NSCLC biology and to discover candidate biomarker(s). Targeted RNA-sequencing revealed new gene fusion transcripts, some clinically relevant gene variants. More over and high FGFR1 mRNA level highly correlated with protein and amplification status in selected cases. Research in progress. Co-funded by the National Centre for Research and Development and CelonPharma within the Strategmed programme.