Molecular and in-silico analysis of single nucleotide polymorphism targeting human TP53 gene exon 5-8 in Sudanese esophageal cancer patients [version 1; peer review: 2 approved]

Abstract

Background: The protein product of the normal TP53 gene performs an essential function in cell cycle control and tumor suppression, and the mutation of a TP53 gene is an essential step in the development of many cancers. Despite the reported association of TP53 gene mutations with many human cancers, the comprehensive computational analysis of single nucleotide polymorphisms (SNPs), and their functional impacts, still remains rare. Methods: In this study DNA were extracted from formalin fixed paraffin embedded samples followed by the conventional polymerase chain reaction and DNA sequencing. Computational analysis was performed using different algorithms to screen for deleterious SNPs. Results: The results demonstrate that there are synonymous SNPs (sSNPs) and non-synonymous SNPs (nsSNPs) in the TP53 gene that may be deleterious to p53 structure and function. Additionally, TP53 gene mutations were found in 40% of samples. Six out of ten of TP53 gene mutations occurred in exon 5, two mutation in exon 6 and other two were present in exon 8. Only one SNP in position E298Q was predicted to have a neutral effect and other SNPs were predicted to be disease related according to Mutation Taster software. A total of 37.2% of squamous cell carcinoma (SCC) samples were found to be mutated, 87.5% of them exist in exon 5, 12.5% in exon 6 and 6.3% in exon 8, whereas adenocarcinoma (AC) achieved a higher rate of mutation (57.1%) with 100% exon 5 involvement. Conclusions: Mutation of TP53 exon 5 in esophageal cancer patients were the most frequent. Genomic results have identified a higher TP53 mutation rate in esophageal AC in contrast to SCC.