title: PAI-1 4G/5G repeat is a target in gastric carcinomas with microsatellite instability.
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.
  
  
  OBJECTIVE
  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%.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Molecular Diagnostics, Department of Laboratory Medicine & Advanced Biotechnologies, IRCCS San Raffaele Pisana, 00163 Rome, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Palmirotta
authors.forename: Fiorella
authors.initials: F
authors.lastname: Guadagni
authors.forename: Annalisa
authors.initials: A
authors.lastname: Savonarola
authors.forename: Giorgia
authors.initials: G
authors.lastname: Ludovici
authors.forename: Gabriella
authors.initials: G
authors.lastname: Nesi
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Mario
authors.initials: M
authors.lastname: Falchetti
authors.forename: Laura
authors.initials: L
authors.lastname: Ottini
mesh_terms: D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm; D005838:Genotype; D006801:Humans; D054643:INDEL Mutation; D053842:Microsatellite Instability; D009154:Mutation; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D017395:Plasminogen Activator Inhibitor 1