Characterization and Prognostic Value of Mutations in Exons 5 and 6 of the P53 Gene in Patients With Colorectal Cancers in Central Iran Publisher



Golmohammadi R¹ ; Namazi MJ¹ ; Nikbakht M² ; Salehi M² ; Derakhshan MH³ Show Affiliations
Source: Gut and Liver Published:2013

Abstract

Background/Aims: We aimed to investigate the relationships among various mutations of the p53 gene and their protein products, histological characteristics, and disease prognosis of primary colorectal cancer in Isfahan, central Iran. Methods: Sixty-one patients with colorectal adenocarcinoma were enrolled in the study. Mutations of the p53 gene were detected by single-stranded conformation polymorphism and DNA sequencing. The protein stability was evaluated by immunohistochemistry. Patients were followed up to 48 months. Results: Twenty-one point mutations in exons 5 and 6 were detected in the tumor specimens of 14 patients (23%). Of those, 81% and 9.5% were missense and nonsense mutations, respectively. There were also two novel mutations in the intronic region between exons 5 and 6. In 11 mutated specimens, protein stability and protein accumulation were identified. There was a relationship between the type of mutation and protein accumulation in exons 5 and 6 of the p53 gene. The presence of the mutation was associated with an advanced stage of cancer (trend, p<0.009). Patients with mutated p53 genes had significantly lower survival rates than those with wild type p53 genes (p<0.01). Conclusions: Mutations in exons 5 and 6 of the p53 gene are common genetic alterations in colorectal adenocarcinoma in central Iran and are associated with a poor prognosis of the disease. Copyright © 2007 by Gut and Liver.