Gut Liver.  2013 May;7(3):295-302. 10.5009/gnl.2013.7.3.295.

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

• Golmohammadi R
• Namazi MJ
• Nikbakht M
• Salehi M
• Derakhshan MH

• KMID: 1431344
• DOI: http://doi.org/10.5009/gnl.2013.7.3.295

Abstract

BACKGROUND/AIMS
We aimed to investigate the relation-ships 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.

Keyword

Colorectal neoplasms; p53 gene mutation; Missense; Nonsense

MeSH Terms

Adenocarcinoma
Codon, Nonsense
Colorectal Neoplasms
Exons
Genes, p53
Humans
Immunohistochemistry
Introns
Iran
Point Mutation
Prognosis
Protein Stability
Sequence Analysis, DNA
Survival Rate
Codon, Nonsense