Expression profiling of driver genes in female never-smokers with non-adenocarcinoma non-small cell lung cancer in China

Abstract Background Although smoking is a primary cause of lung cancer, females are overrepresented among never-smokers with the disease. The mutational landscape of adenocarcinoma in never-smoking females has been extensively profiled; however, there is little knowledge about genomic alterations in non-adenocarcinoma non-small cell lung cancer (NA-NSCLC). In the study, we reviewed the status of oncogenic drivers of NA-NSCLC in these populations. Materials and Methods Comprehensive genomic profiling was performed on DNA extracted from formalin-fixed, paraffin-embedded sections of 52 NA-NSCLC tissues, including 35 squamous cell carcinomas (SQCCs), 11 adenosquamous carcinomas (ASC), 5 pulmonary sarcomatoid carcinoma (PSC), and 1 large cell carcinoma by next-generation sequencing within a panel of 68 cancer-related genes. Results Mutations of the common oncogenic drivers (EGFR, KRAS, ALK, ROS1, MET, RET, and ERBB2) occurred in 61.5% of cases. The frequency of well-established targets (EGFR and ALK), new targets without widely available therapies (MET and ERBB2) and potentially actionable targets (RET and DDR2) in SQCCs of female never-smokers, was significantly higher than that in The Cancer Genome Atlas dataset. There were 31%, 82%, and 80% of cases with SQCC, ASC, and PSC, respectively, harboring at least one of the following targets: EGFR, ALK, ERBB2, and MET. Approximately 78% (7/9) of the patients responded to various targeted treatments. Conclusion Female never-smokers with NA-NSCLC in this study had a high frequency of currently known or potentially actionable oncogenic alterations and could benefit from targeted therapy. Our study also provides evidence for the recommendation of molecular analysis in never-smoking female SQCC.