A single-center, cohort study of the mutational profile of Ukrainian patients with non-small cell lung cancer

Background. Lung cancer continues to be a significant health concern globally. Due to the heterogeneity of the disease, using innovative strategies for effective management and treatment of patients is extremely important. Purpose – to characterize the mutational profile of a group of non-small cell lung cancer (NSCLC) patients utilizing a next-generation sequencing technique. Materials and Methods. A total of 42 samples that were fixed in formalin and embedded in paraffin (FFPE) were collected from 42 Ukrainian patients diagnosed with lung cancer who had surgery at the Sumy Regional Clinical Oncology Center. DNA was extracted from FFPE samples using the Omega Bio-tek E.Z.N.A.® FFPE DNA Kit (USA) following the manufacturerʼs instructions. Sequencing was performed on the Illumina NextSeq 550Dx platform (USA) using the Illumina NextSeq 550 Mid-Output Kit. The Cancer Genome Atlas Program (TCGA) database (https://portal.gdc.cancer.gov/) was used for a comparative analysis of the prevalence of genomic mutations in a cohort of Ukrainian and Caucasian patients with NSCLC. Statistical analysis was performed using Stata V.18.0 software (StataCorp, Texas, USA; https://www.stata.com; 2024). The paper belongs to the «description of case series» category which is a type of study recognized by evidence based medicine and does not claim statistical significance of the result. Results. Among the 42 NSCLC samples, 11 (26.19%) carried driver mutations such as EGFR (n=2; L858R), KRAS (n=7; G12C, G12D, G12A and A146S), BRAF (n=1; V600E) and translocation EML4(exon6) – ALK (exon20) (n=1; chr2:42503838 – chr2:29447579). All mutations were mutually exclusive. No NRAS, ROS1, RET, MET, ERBB2, and PIK3CA mutation cases were detected. The number of driver mutations in patients who had never smoked was significantly higher than in former or current smokers (p=0.046). No association was found between age, sex, tumor stage, histology of NSCLC, and driver mutations. Conclusions. Molecular genetic profiling using next-generation sequencing revealed driver mutations in 26.19% of patients with radically treated NSCLC. Most mutations are oncogenic and sensitive to tyrosine kinase inhibitors.