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Gut and Liver

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Characterization and Prognostic Value of Mutations in Exons 5 and 6 of the p53 Gene in Patients with Colorectal Cancers in Central Iran

Rahim Golmohammadi*, Mohammad J. Namazi*, Mehdi NikbakhtΆΣ, Mohammad SalehiΆΣ, and Mohammad H. DerakhshanΆΤ
*Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, ΆΣFaculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran, and ΆΤSection of Gastroenterology, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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. (Gut Liver 2013;7:295-302)
 
KEYWORD
Colorectal neoplasms; p53 gene mutation; Missense; Nonsense
 
Gut and Liver 2013 May; 7(3): 295-302
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