Implication of exon 4 TP53 Gene mutations in colorectal cancers in Senegalese patients

Abstract

Background: Colorectal cancer (CRC) is a major cause of death in men and women, comprising about 10% of cancer deaths after breast and lung cancer. The most significant risk factors currently implicated in the etiology of this cancer are genetic, likely due to several mutations. Methods: The study explored the involvement of genetic factors in these pathologies; specifically, exon 4 of the TP53 gene was studied in 15 CRC patients and compared with 10 healthy individuals as controls. The position of the marker mutations was determined with the Mutation Surveyor software version 5.1.2. DnaSP version 5.10, MEGA version 7.014, and the program Arlequin version 3.1 were used to highlight the parameters of variability, differentiation, and the demo-genetic evolution of our study populations. The pathogenicity of the mutations was determined through Polyphen2, TAMISER, and ClinVar. Results: Our results showed the presence of a recurrent mutation of the TP53 gene in both tumor and healthy tissue where proline was replaced with arginine at codon 72. This mutation was predicted to be benign. The presence of this mutation in healthy tissue can be considered a relatively late event in colorectal tumorigenesis. In addition, the P47L, D49A, W53S, and D48G mutations appeared to be suspicious because they were predicted to be potentially damaging. This finding suggests the genes’ involvement in the pathology of CRCs in our study population. The cancer tissue sequences contained an average of 2.59 nucleotide differences that resulted in amino acid changes. The Nei genetic distance confirms this variability between tumor tissues. Conclusion: These results suggest that variants in exon 4 of the TP53 gene may contribute to the development of CRCs. These mutations could constitute molecular markers in CRC and possibly help in the development of early diagnosis