摘要
Objective:Dysfunction in fibroblast growth factor receptor(FGFR)signaling has been reported in diverse cancer types,including non-small cell lung cancer(NSCLC).The frequency of FGFR aberrations in Chinese NSCLC patients is therefore of great clinical significance.Methods:A total of 10,966 NSCLC patients whose tumor specimen and/or circulating cell-free DNA(cf DNA)underwent hybridization capture-based next-generation sequencing were reviewed.Patients'clinical characteristics and treatment histories were also evaluated.Results:FGFR aberrations,including mutations,fusions,and gene amplifications,were detected in 1.9%(210/10,966)of the population.FGFR abnormalities were more frequently observed in lung squamous cell carcinomas(6.8%,65/954)than lung adenocarcinomas(1.3%,128/9,596).FGFR oncogenic mutations were identified in 19 patients(~0.17%),of which,68%were male lung squamous cell carcinoma patients.Eleven out of the 19 patients(58%)had concurrent altered PI3 K signaling,thus highlighting a potential combination therapeutic strategy of dual-targeting FGFR and PI3 K signaling in such patients.Furthermore,FGFR fusions retaining the intact kinase domain were identified in 12 patients(0.11%),including 9 FGFR3-TACC3,1 FGFR2-INA,1 novel FGFR4-RAPGEFL1,and 1 novel fusion between the FGFR1 and SLC20 A25′-untranslated regions,which may have caused FGFR1 overexpressions.Concomitant EGFR mutations or amplifications were observed in 6 patients,and 4 patients received anti-EGFR inhibitors,in whom FGFR fusions may have mediated resistance to anti-EGFR therapies.FGFR amplification was detected in 24 patients,with the majority being FGFR1 amplifications.Importantly,FGFR oncogenic mutations,fusions,and gene amplifications were almost always mutually exclusive events.Conclusions:We report the prevalence of FGFR anomalies in a large NSCLC population,including mutations,gene amplifications,and novel FGFR fusions.
基金
supported by the National Key R&D Program of China(Grant No.2016YFC1303800)。
