DISRUPTIVE AND TRUNCATING TP53 MUTATIONS ARE ASSOCIATED WITH AFRICAN-ANCESTRY AND WORSE PROGNOSIS IN BRAZILIAN PATIENTS WITH LUNG ADENOCARCINOMA

Introduction: TP53 is the most mutated gene in lung tumors. However, its prognostic role remains unclear, mainly in admixed populations. Objective: We aimed to evaluate the frequency and clinicopathological impact of TP53 mutations in Brazilian non-small cell lung cancer (NSCLC) patients. MATERIALS AND Methods: We analyzed 446 NSCLC patients. TP53 mutational status was evaluated by targeted NGS and biologically classified as disruptive/nondisruptive, and as truncating/non-truncating. Genetic ancestry was assessed using 46-ancestry informative markers. Analysis of lung adenocarcinomas from the cBioportal dataset was performed. TP53 mutations were associated with patients’ clinicopathological features. Results: TP53 mutations were detected in 64.3% (287/446) of NSCLC cases. For lung adenocarcinomas, TP53 mutations were detected in 60.4% (n=221/366) of cases. TP53 mutations were associated with younger age and brain metastasis at diagnosis, tobacco consumption, and higher African ancestry. TP53 mutations were associated with younger age and Black skin color in cBioportal datasets. Patients harboring disruptive/truncating TP53 mutations had worse overall survival than nondisruptive/non-truncating and wild-type patients. Conclusion: TP53 mutations are common in Brazilian lung adenocarcinomas, and their biological characterization as disruptive and truncating mutations is associated with African ancestry and shorter overall survival.