RT Journal Article SR Electronic T1 Genetic analysis of TP53 gene mutations in exon 4 and exon 8 among esophageal cancer patients in Sudan JF bioRxiv FD Cold Spring Harbor Laboratory SP 572214 DO 10.1101/572214 A1 Sulafa Mohamed Eltaher A1 Abeer Babiker Idris A1 A. H Mahmoud A1 Mawadah Yousif Mohamed Yousif A1 Nouh Saad Mohamed A1 Muzamil M. Abdel Hamid A1 Kamal Elzaki Elsiddig A1 Galal Mohammed Yousif A1 Mohamed A. Hassan YR 2019 UL http://biorxiv.org/content/early/2019/03/09/572214.abstract AB Background Esophageal carcinoma (EC) represents the 1st rank among all gastrointestinal cancers in Sudan. Despite little publications, there is a deep absence of literature about the molecular pathogenesis of EC considering TP53 gene from Sudanese population.Aims In this study, we performed the expression analysis on p53 protein level by immunohistochemical 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 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 in bioinformatics tools.Result Nuclear accumulations for p53 protein was detected in all of the esophageal carcinomas examined while no accumulations were observed in normal control sections. Four patients with 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 subject 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 were observed.Conclusion we found a significant association between the overexpression of TP53 protein and mutation in exon 4 and 8. A silent mutation P301P was detected in all of examined cases. Two patients who diagnosed with small cell sarcoma have shared the same mutations in exon8. Further studies with large sample size are required to demonstrate the usefulness of these mutations in the screening of EC especially SCCE.