Background: Lung cancer remains one of the most diagnosed malignancies, being the second most diagnosed cancer, while still being the leading cause of cancer-related deaths. Late diagnosis remains a problem, alongside the high mutational burden encountered in lung cancer. Methods: We assessed the genetic profile of cancer genes in lung cancer using The Cancer Genome Atlas (TCGA) datasets for mutations and validated the results in a separate cohort of 32 lung cancer patients using tumor tissue and whole blood samples for next-generation sequencing (NGS) experiments. Another separate cohort of 32 patients was analyzed to validate some of the molecular alterations depicted in the NGS experiment. Results: In the TCGA analysis, we identified the most commonly mutated genes in each lung cancer dataset, with differences among the three histotypes analyzed. NGS analysis revealed TP53, CSF1R, PIK3CA, FLT3, ERBB4, and KDR as being the genes most frequently mutated. We validated the c.1621A>C mutation in KIT. The correlation analysis indicated negative correlation between adenocarcinoma and altered PIK3CA (r = −0.50918; p = 0.0029). TCGA survival analysis indicated that NRAS and IDH2 (LUAD), STK11 and TP53 (LUSC), and T53 (SCLC) alterations are correlated with the survival of patients. Conclusions: The study revealed differences in the mutational landscape of lung cancer histotypes.

Centre for Molecular Medicine Central European Institute of Technology Masaryk University 62500 Brno Czech Republic

Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute Faculty of Medicine Masaryk University 62500 Brno Czech Republic

Department of Pharmaceutical Sciences University of Vienna 1010 Vienna Austria

Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences 05 552 Magdalenka Poland

Institute of Neurobiology Bulgarian Academy of Sciences 1113 Sofia Bulgaria

Leon Daniello Pulmonology Hospital 400332 Cluj Napoca Romania

Ludwig Boltzmann Institute for Digital Health and Patient Safety Medical University of Vienna 1090 Vienna Austria

Regional Institute of Gastroenterology and Hepatology 400000 Cluj Napoca Romania

Research Center for Functional Genomics Biomedicine and Translational Medicine Iuliu Hatieganu University of Medicine and Pharmacy 400337 Cluj Napoca Romania

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