Genetic Analysis of TP53 Gene Mutations in Exon 4 and Exon 8 among Esophageal Cancer Patients in Sudan

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Sulafa Mohamed Eltaher
AbeerBabiker Idris
Mahmoud A. H
MawadahYousif Mohamed Yousif
Muzamil M. Abdel Hamid
Kamal Elzaki Elsiddig
Galal Mohammed Yousif
Mohamed A. Hassan
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Napata College
Background: Esophageal Carcinoma (EC) represents the firstrank among all gastrointestinalcancers in Sudan. There are few publications in which there is an absence of literature about themolecular pathogenesis of EC considering TP53 gene from Sudanese population. Aims: In this study we performed the expression analysis on p53 protein level byimmuno-histochemical staining and examined its overexpression with p53 mutations in exons 4 and 8 among esophageal cancer patients in Sudan. Material and Methods: Fixed tissue with 10% buffered formalin was stained by Hematoxlinand Eosin (H&E), Alcian blue- Periodic Acid Schiff (PAS) and immunohistochemistry stain.PCRRFLP was used to study the frequencies of p53 codon 72 R/P polymorphism. ConventionalPCR and Sanger sequencing were applied for exon 4 and exon 8. Then detection and functionalanalysis of SNPs and mutations were performed using various bioinformatics tools. Results: Nuclear accumulations for p53 protein was detected in all of the esophageal examined carcinomas, while no accumulations were observed in normal control sections. Four patients that were immune-positive for p53 showed no mutations in p53 gene (exon4 and exon8). The incidence ofthe homozygous mutant variant Pro/Pro was higher in esophageal cancerous patients comparingto healthy control subjects 20(71. 4%) vs. 1(10%), respectively (p=0.0026). In exon 4, nomutation was detected other than NG_017013.2:g. 16397C>G. While in exon 8, g.18783-18784AG>TT, g.18803A>C, g.18860A>C, g.18845A>T and g.18863_ 18864 InsT wereobserved. Conclusion: We found a significant association between the overexpression of TP53 protein andmutations in exon 4 and 8. A silent mutation P301P was detected in all of examined cases. Twopatients who were diagnosed with small cell sarcoma shared the same mutations in exon8.Further studies with a larger sample size are required to demonstrate the usefulness of thesemutations in the screening of EC especially SCCE.