TP53 Codon 72 Heterozygosity May Promote MicrosatelliteInstability in Sporadic Colorectal Cancer
Objective: The polymorphic variants at codon 72 of the p53 gene, encoding prolineor arginine at residue 72, produce marked changes in the p53 structure. From theevidence that the DNA mismatch repair system and p53 interact to maintain genomicintegrity, we hypothesized that codon 72 variations may in...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Royan Institute (ACECR), Tehran
2010-01-01
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| Series: | Cell Journal |
| Subjects: | |
| Online Access: | http://celljournal.org/library/upload/article/4%20Nikhbakht.pdf |
| Summary: | Objective: The polymorphic variants at codon 72 of the p53 gene, encoding prolineor arginine at residue 72, produce marked changes in the p53 structure. From theevidence that the DNA mismatch repair system and p53 interact to maintain genomicintegrity, we hypothesized that codon 72 variations may influence the prevalence ofmicrosatellite instability (MSI), a feature of malignancies associated with mismatchrepair deficiency in sporadic colorectal cancer.Materials and Methods: We investigated the frequency of MSI in three P53 codon72 genotypes using genomic DNAs from 144 paraffin blocks of sporadic colorectaladenocarcinomas by testing the BAT-26 poly(A) marker. We used PCR-SSCP analysisto detect tumor sample MSI for the nonisotopic detection of deletions in the BAT-26 poly (A) mononucleotide repeat. Associations between qualitative variables wereevaluated using the χ2-test. Statistical significance level was set to p ≤ 0.05.Results: MSI analysis revealed that 24.3% of the tumors (n=35) were MSI-positiveand 75.7% (n=109) were MSI-negative. The frequency of microsatellite instability inthe arginine/arginine, arginine/proline and proline/proline genotypes were 11 (16.9%),22 (36.1%) and 2 (11.1%) respectively. A significant difference in distribution of MSIwas found for the arginine/proline genotype compared with the grouped arginine/arginineand proline/proline genotypes (p=0.05).Conclusion: Our findings suggested that colorectal adenocarcinomas arising in individualswith the p53 codon 72 arginine/proline heterozygosity are more prone tomicrosatellite instability than those with other p53 genotypes. In our study, MSI wasimportant in the carcinogenesis of sporadic colorectal cancer arising in pro/arg heterozygotes. |
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| ISSN: | 2228-5806 2228-5814 |