TY - JOUR
T1 - PAI-1 4G/5G repeat is a target in gastric carcinomas with microsatellite instability
AU - Palmirotta, Raffaele
AU - Guadagni, Fiorella
AU - Savonarola, Annalisa
AU - Ludovici, Giorgia
AU - Nesi, Gabriella
AU - Palli, Domenico
AU - Falchetti, Mario
AU - Ottini, Laura
PY - 2011/6
Y1 - 2011/6
N2 - 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.
AB - 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.
KW - Gastric cancer
KW - PAI-1 4G/5G polymorphism
KW - Plasminogen activator inhibitor-1
UR - http://www.scopus.com/inward/record.url?scp=79955921095&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79955921095&partnerID=8YFLogxK
U2 - 10.1016/j.dld.2010.12.002
DO - 10.1016/j.dld.2010.12.002
M3 - Article
C2 - 21216681
AN - SCOPUS:79955921095
VL - 43
SP - 454
EP - 458
JO - Digestive and Liver Disease
JF - Digestive and Liver Disease
SN - 1590-8658
IS - 6
ER -