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KMID : 1188320130070030295
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Gut and Liver
2013 Volume.7 No. 3 p.295 ~ p.302
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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
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Rahim Golmohammadi
Mohammad J. Namazi
Mehdi Nikbakht
Mohammad Salehi
Mohammad H. Derakhshan
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Abstract
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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.
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KEYWORD
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Colorectal neoplasms, p53 gene mutation, Missense, Nonsense
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