Characterization and Prognostic Value of Mutations in Exons 5 and 6 of the p53 Gene in Patients with Colorectal Cancers in Central Iran.
- Author:
Rahim GOLMOHAMMADI
1
;
Mohammad J NAMAZI
;
Mehdi NIKBAKHT
;
Mohammad SALEHI
;
Mohammad H DERAKHSHAN
Author Information
- Publication Type:Original Article
- Keywords: Colorectal neoplasms; p53 gene mutation; Missense; Nonsense
- MeSH: Adenocarcinoma; Codon, Nonsense; Colorectal Neoplasms; Exons; Genes, p53; Humans; Immunohistochemistry; Introns; Iran; Point Mutation; Prognosis; Protein Stability; Sequence Analysis, DNA; Survival Rate
- From:Gut and Liver 2013;7(3):295-302
- CountryRepublic of Korea
- Language:English
- 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.
