Prognosis and Functional Analyzes of Missense Mutations in Exon 4 of the TP53 Gene in Colorectal Cancer in the Senegalese Population

Colorectal cancer is a complex and multifactorial pathology, the progression of which involves genetic mutations affecting the p53 protein, a key regulator of tumor suppression.This study focused on identifying, characterizing, and evaluating the pathogenicity of missense mutations (nsSNPs) in exon 4 of the TP53 gene in Senegalese patients suffering from colorectal cancer.The analysis of 24 patients and 24 controls revealed 13 new variants, including 11 located in the transactivation domain TAD2 one in the proline-rich domain, and one in the DNA-binding domain.Among these mutations, some alter the stability and function of the p53 protein, while others, such as the recurrent polymorphism at codon 72 (p.P72R), are considered benign.Post-translational modifications, such as the loss of phosphorylation at S46 and the gain of phosphorylation at T55, were also observed, influencing p53 activity.Although no major structural changes were predicted for the p53 protein, conformational changes at binding sites were detected for certain mutants (p.D48V, p.D48N, p.D59A, p.I50F, p.Q52E, and p.P72R).These results highlight the potential pathogenic role of these mutations in colorectal cancer in Senegal and shed light on the importance of genetic variability in colorectal tumorigenesis.