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Microsatellite instability in intracranial meningioma and the involvement of MLH1 and MSH2 mismatch repair genes

Genomic instability is a prominent characteristic of tumor cells and the result of defective DNA repair mechanisms. The defects in the functioning of postreplicative mismatch repair (MMR) gives rise to microsatellite instability (MSI). In the present study two major MMR genes, MLH1 and MSH2, were investigated in a group of 50 human intracranial meningeomas. The tumors were analyzed with microsatellite markers amplified by polymerase chain reaction (PCR) and visualized by gel electrophoresis on high resolution gels. Furthermore, MSI was also investigatedfor genes DVL3, AXIN1 and CDH1. Our study revealed that 38% of our total meningeomas sample showed MSI at one microsatellite locus, 16% on two and 13.3% on three loci when compared to the autologous blood DNA. The percent of detected MSI for MSH2 gene was 14% and for MLH1 it was 26%, for DVL3 22.9%, for AXIN1 17.8% and for CDH1 8.3%. The markers employed also detected gross deletions of MLH1 gene in 24% of meningeomas. Genetic changes between MLH1 and MSH2 were significantly positively correlated (P=0.032). We also noted a positive correlation between genetic changes of MSH2 and DVL3 genes (P=0.034). Genetic changes in DVL3 were strongly associated with anaplastic histology ofmeningioma (χ2=9.14, P=0.01). Our study discovered constant presence of MSI in meningioma patients which indicates that MMR, the mechanism that safeguards the stability of our genome, is defective in human intracranial meningiomas. The importance of MSI phenotype in human tumors is an emerging field demonstrating its involvement in the clinical course of the disease, response to therapy and survival outcomes.

MSI, meningioma, MSH2, MLH1

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