First Insight into the Mutational Landscape of BRAF and KRAS Genes in Lung Cancer Patients from Morocco

Abstract

Background/Introduction: Lung cancer (LC) is a lethal malignancy with a late diagnosis and poor prognosis. During the last decade, the identification of oncogenic driver alterations has noticeably changed the therapeutic landscape and contributed to the emergence of the “oncogene addiction” concept and precision medicine in oncology. Among these alterations, the spotlight has turned to driver mutations in the KRAS and BRAF genes, which have garnered significant attention due to the emergence of targeted therapies and the potential for personalized treatment strategies. Objective: Hence, the present study aimed to evaluate the mutational landscape of the KRAS and BRAF genes in LC Moroccan patients along with their frequencies and their correlation with clinicopathological features. Methods: A total of 60 fresh biopsies were collected from patients with primary LC and were subjected to PCR-DNA sequencing of exon 2 of KRAS and exon 15 of BRAF genes in order to detect the most common mutations known by their implication in response to targeted therapies. Results and Discussion: Sequencing analysis revealed that mutations in KRAS and BRAF genes represented respectively 8.3% and 6.7% of cases; one patient had two KRAS mutations (G12A and K5E), and none had simultaneous BRAF and KRAS mutations. The vast majority of patients harboring KRAS mutations were men, formal smokers with adenocarcinomas, and at advanced stage (stage III). BRAF mutations were mainly detected in men and non-smokers with adenocarcinoma. Statistical analyses showed no significant correlation between KRAS and BRAF substitutions and clinico-pathological features (p>0.05). Conclusion: The presence of these mutations will be used as a valuable molecular biomarker to select potential candidates eligible for effective personalized therapy using available agents targeting these mutations. However, much effort is needed to identify other druggable mutations to generalize personalized LC therapy for better management of this devastating disease.