PAI-1 4G/5G repeat is a target in gastric carcinomas with microsatellite instability
| Autor: | Domenico Palli, Annalisa Savonarola, Raffaele Palmirotta, Laura Ottini, Fiorella Guadagni, Mario Falchetti, Giorgia Ludovici, Gabriella Nesi |
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| Rok vydání: | 2011 |
| Předmět: |
Genotype
DNA repair DNA Mutational Analysis gastric cancer plasminogen activator inhibitor-1 pai-1 4g/5g polymorphism medicine.disease_cause Polymorphism Single Nucleotide INDEL Mutation Stomach Neoplasms Polymorphism (computer science) Plasminogen Activator Inhibitor 1 Humans Medicine Mutation frequency Gene Mutation Hepatology business.industry Gastroenterology Microsatellite instability DNA Neoplasm medicine.disease Molecular biology digestive system diseases Allelic Imbalance Microsatellite Instability business |
| Zdroj: | Digestive and Liver Disease. 43:454-458 |
| ISSN: | 1590-8658 |
| Popis: | Background The plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathogenesis of cancer. The 4G/5G promoter polymorphism of PAI-1 is potentially involved in regulating gene transcription. Aims To explore the role of the PAI-1 4G/5G repeat as target of microsatellite instability (MSI), 50 gastric carcinomas (GCs), characterized for MSI, were screened. Methods PAI-1 4G/5G was analysed by direct sequencing. Results Allelic imbalance was observed in 5 of the 50 (10%) GCs. Specifically, 2 cases (40%) harboured a G deletion and 3 (60%) a G insertion in tumour compared to normal DNA. These five cases were included in the subgroup of 20 GCs (25%) with high level of MSI (MSI-H). A statistically significant association emerged between PAI-1 mutations and MSI-H status (p = 0.0073). The frequency of PAI-1 mutations was also evaluated, together with other known target genes, by analysing MSI-H GCs for mutations at selected coding repeats within genes controlling cell growth, apoptosis and DNA repair. Overall, mutation frequency ranged from 56.3% to 5.3%. Conclusion The frequency of PAI-1 mutations here reported in MSI-H GCs is, accordingly, comparable with values obtained for real targets. The relatively high incidence of PAI-1 mutations is suggestive of a positive pressure towards selection in MSI-H GCs. |
| Databáze: | OpenAIRE |
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