Genetic Analysis of TP53 Gene Mutations in Exon 4 and Exon 8 among
Esophageal Cancer Patients in Sudan
Sulafa Mohamed Eltaher1*, Abeer Babiker Idris2,3, Mahmoud A. H4 , Mawadah Yousif Mohamed Yousif4, Muzamil M. Abdel Hamid4 , Kamal Elzaki Elsiddig5, Galal Mohammed Yousif6, Mohamed A. Hassan3,7 1The Academy of Health Sciences, the Republic of Sudan Federal Ministry of Health, Khartoum, Sudan 2Department of medical microbiology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan. 3Applied Bioinformatics Center, Africa City of Technology, Khartoum, Sudan 4Department of Parasitology and Medical Entomology, Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan. 5Department of Surgery, Faculty of Medicine, University of Khartoum, Khartoum, Sudan. 6Faculty of Pharmacy, Alrebat University, Khartoum, Sudan 7Department of Bioinformatics, DETAGEN Genetic Diagnostics Center, Kayseri, Turkey
* Corresponding author: Sulafa Mohamed Eltaher, Assistant Professor. The Academy of Health Sciences, The Republic of Sudan Federal Ministry of Health, Khartoum, Sudan.
Received: 1 September 2022
Accepted: 10 September 2022
Background: Esophageal Carcinoma (EC) represents the first rank among all gastrointestinal
cancers 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 by immuno histochemical staining and examined its over expression 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 Hematoxlin and Eosin (H&E), Alcian blue- Periodic Acid Schiff (PAS) and immunohistochemistry stain.
PCR-RFLP was used to study the frequencies of p53 codon 72 R/P polymorphism. Conventional PCR and Sanger sequencing were applied for exon 4 and exon 8. Then detection and functional analysis of SNPs and mutations were performed using various bioinformatics tools.
Results: Nuclear accumulations for p53 protein were 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 of the homozygous mutant variant Pro/Pro was higher in esophageal cancerous patients comparing to healthy control subjects 20(71. 4%) vs. 1(10%), respectively (p=0.0026).In exon 4, no mutation 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
Conclusion: We found a significant association between the over expression of TP53 protein and mutations in exon 4 and 8. A silent mutation P301P was detected in all of examined cases. Two patients 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 these mutations in the screening of EC especially SCCE.
Key words: Esophageal carcinoma, Small cell carcinoma, SNPs, functional analysis, in silico tools
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