Abstract
Fusions have been described in the fibroblast growth factor receptors (FGFR) 1-3 genes with multiple partners in a variety of tumors. Here we focused on the prevalence of FGFR fusions in lung cancers for whom might benefit from FGFR inhibitors in clinical development. We reviewed FGFR alterations in 10833 lung cancer patients (pts) who underwent genetic testing at our institute from 2016 to 2019. Mutation profiles were analyzed using hybridization capture based next-generation sequencing (NGS), which covers all exons of FGFR1-3 and specific intron regions containing the break points of fusions. All patients were also analyzed for mutations in EGFR, KRAS, HER2, BRAF, ALK, RET, MET, ROS1, as well as other oncogenes. FGFR fusions were identified in 25 lung cancer pts, including 9 adenocarcinoma pts, 4 squamous-cell carcinoma pts, 1 patient with large cell neuroendocrine carcinoma and 11 pts with non-specific pathology. FGFR3-TACC3 fusion was detected in 72% (18/25) of pts and the remaining were previously unreported fusions (table). Concurrent EGFR mutations were identified in 44% (11/25) of pts with FGFR fusions (32%, treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs); 12%, not treated with EGFR-TKIs). PI3K-AKT-MTOR signaling pathway was also activated in 28% (7/25) of pts, and cell-cycle gene alterations were also detected in 16% (4/25) of pts.TableFrequency of FGFR fusionsFusionsFusion regionN (%)FGFR3-TACC3EX17:EX116 (24%)EX18E:EX114 (16%)EX18E:EX132 (8%)EX17:EX102 (8%)others4 (16%)FGFR1-chr8:21672159EX1:chr8:216721591 (4%)FGFR1-MTUS1EX19E:EX81 (4%)EFHA2-FGFR1EX2:EX31 (4%)TNRC18-FGFR1PMT:EX101 (4%)ZMAT4-FGFR1EX2:EX21 (4%)ZNF696-FGFR1EX2:EX18E1 (4%)OPALIN-FGFR2EX6E:EX21 (4%)Total25 (100%) Open table in a new tab FGFR1-3 fusions define a unique molecular subtype of lung cancer. Depending on the concurrent genetic alterations, combined targeted therapy might be an optimal strategy to control tumor growth for these pts.
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