Frequency and Characterization of TP53 Tumor Suppressor Gene Mutations in the Development and Progression of Prostate Tumors in Senegal

Prostate tumors are more common worldwide, with 60% of men over the age of 50 affected by benign prostatic hyperplasia (BPH) and 1.5 million new cases and 397,000 deaths from prostate cancer (PCa), which ranks as the second most common cancer globally. Although age is the most significant factor, other factors are associated with their development, and genetic factors appear to play a major role. This study aimed to evaluate the involvement of TP53 gene mutations in cases of prostate tumors among Senegalese men while contributing to the understanding of the mutational link between the two tumors. sixteen BPH tissue samples and seventeen PCa tissue samples were collected via biopsy from Senegalese patients following informed consent. DNA extraction followed by PCR amplification and sequencing were performed. Mutation Surveyor was used to identify mutations. Mutation Taster, Polyphen-2, SIFT, and SNP & GO were used to assess pathogenicity predictions. I-Mutant2, MuPro, and Dynamut2 were used to predict the stability, flexibility, and dynamics of the mutated p53 protein. MutPred2 and Mutation3D were used to predict physicochemical properties and map risk mutations. Variability, diversity, and genetic structure were determined using MEGA, BioEdit, DnaSP, and Arlequin. A total of 32 TP53 mutations were identified in the two tumors. These mutations were predominant in prostate cancer. No mutations shared between the two tumor types were found; however, shared mutations within each tumor type were observed, particularly one mutation (c.652G>A p.218Val>Met) present in all prostate cancer patients. Most non-synonymous mutations are predicted to be pathogenic and destabilizing for the mutated p53 protein in both tumors. Low polymorphism and a short genetic distance were observed between the two prostate tumors. This study provided insight into the potential impact of TP53 gene mutations on prostate tumors. Despite their low frequency in the Senegalese population, which may be explained by the small sample size, they play a role in the development and aggressiveness of prostate tumors. Therefore, special attention is required in patients carrying these mutations, particularly for the c.652G>A p.218Val>Met mutation, as the latter could influence management.