engleski

Microsatellite instability signatures in human meningioma

The defect in the functioning of the postreplicative mismatch repair (MMR) increases the genome’s overall mutational frequency and is reflected in a phenomenon called microsatellite instability (MSI). MSI can be detected by the microsatellite gene markers and the instability is evident from different numbers of microsatellite repeats in tumor tissue when compared to normal blood DNA. One of the major mismatch repair genes - MLH1 is responsible for MMR and when mutated or lost the system does not work correctly. We decided to investigate if MMR gene MLH1 is associated with the overall frequency of MSI. The overall MSI on 7 different loci in the genome of 35 meningioma patients of different histopathological subtypes and grades was investigated and compared to large deletions of the MLH1 gene. Microsatellite markers used were: D3S1611, D16S3399, D3S1262, D16S752, D16S3025, D18S66, and D18S819. Large deletion of MLH1 was analyzed by the loss of heterozygosity (LOH) method. A relatively high presence of microsatellite instability in meningioma patients, when compared to their autologous blood DNA, was detected. 25 patients showed MSI at least one of the seven different investigated loci of the genome (71.4%). MLH1 was struck by large deletion or LOH in 7 meningioma cases (20%). When comparing overall MSI to the LOH of the MLH1 gene we found that four cases that harbored MLH1 deletions also showed MSI (57.1%). However, MSI was not associated with any histological subtype and was evenly distributed among different grades. The found deletions of the MLH1 gene indicate malfunctioning of the MMR system in investigated meningiomas. This was further supported by the relatively high overall incidence of MSI. Our study helps to better understand the genetic profile of human meningiomas and may shed information on the clinical course, response to therapy, and survival outcomes.

meningioma ; microsatellite instability (MSI) ; mismatch repair (MMR), MLH1, loss of heterozygosity

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