Expression Profiling of Driver Genes in Female Never-smokers With Non-adenocarcinoma Non-small-cell Lung Cancer in China.

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, 5 pulmonary sarcomatoid carcinoma, 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, adenosquamous carcinoma, and pulmonary sarcomatoid carcinoma, 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.