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22 May 2003

Genotyping of p53 codon 175 in colorectal cancer

Wanda M. Krajewska, Magdalena Stawińska, Magdalena Bryś, Wojciech Młynarski, Henryk Witas, Andrzej Okruszek, Zofia M. Kiliańska

Med Sci Monit 2003; 9(5): BR188-191 :: ID: 11060

Abstract

Background: The gene encoding the tumor suppressor protein p53 is one of the most frequently mutated in human cancer. Over 8000 mutations of this gene have been identified. The spectrum of
p53 mutations varies among tumor types. More than half of these mutations appear in three hotspot codons: 175, 248 and 273. The purpose of the present study was to evaluate the GÆA
transition in codon 175 of the p53 gene as a potential marker of colon cancer progression.
Material/Methods: The prognostic significance of alterations in codon 175 exon 5 of p53 gene was studied in 32 patients with colorectal cancer. The ASA-PCR method was used to assess GÆA (ArgÆHis)
transition in codon 175.
Results: The analyzed point mutation was identified in 56% of the tested cases of colorectal cancer. The frequency of codon 175 p53 gene mutation was found to increase with cancer aggressiveness.
Screening for the studied point mutation in codon 175 showed no alteration in analyzed samples classified as Dukes’ A stage, while variations were observed in 43%, 50% and 75% of the cases classified as Dukes’ B, C, and D, respectively. In three cases the studied mutation was also found in some mucosal cells obtained from resectional borders.
Conclusions: The GÆA transition in codon 175 of the p53 gene may be useful as a potential marker of colorectal cancer progression and as a means of evaluating the margins of surgical resection.

Keywords: Amino Acid Substitution, Base Sequence, Codon - genetics, Colorectal Neoplasms - genetics, DNA, Neoplasm - genetics, Genes, p53, Genotype, Point Mutation, Tumor Markers, Biological - genetics

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750