PAI-1 4G/5G repeat is a target in gastric carcinomas with microsatellite instability

Raffaele Palmirotta, Fiorella Guadagni, Annalisa Savonarola, Giorgia Ludovici, Gabriella Nesi, Domenico Palli, Mario Falchetti, Laura Ottini

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)454-458
Number of pages5
JournalDigestive and Liver Disease
Volume43
Issue number6
DOIs
Publication statusPublished - Jun 2011

Keywords

  • Gastric cancer
  • PAI-1 4G/5G polymorphism
  • Plasminogen activator inhibitor-1

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

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    Palmirotta, R., Guadagni, F., Savonarola, A., Ludovici, G., Nesi, G., Palli, D., Falchetti, M., & Ottini, L. (2011). PAI-1 4G/5G repeat is a target in gastric carcinomas with microsatellite instability. Digestive and Liver Disease, 43(6), 454-458. https://doi.org/10.1016/j.dld.2010.12.002