Genetic instability in myelodysplastic syndrome: Detection of microsatellite instability and loss of heterozygosity in bone marrow samples with karyotype alterations

Abstract

Using a polymerase chain reaction (PCRI)-based approach, we examined the prevalence of loss of heterozygosity (LOH) and microsatellite instability (MSI)in relation to chromosomal imbalances in myelodysplastic syndrome (MDS). Two of 26 patients displayed MSI (8%), one of them at five loci. LOH was detected in six out of 26 cases (23%), predominantly involving markers IRF1 [5q31] and WT1 [11p]. Two patients displayed a corresponding chromosomal deletion by conventional cytogenetics. Supporting the mutator phenotype hypothesis, a significant coincidence of LOH, MSI and chromosome abnormalities was observed (P < 0·025). Moreover, our data suggest that LOH represents an initial rather than a secondary genetic event in MDS, promoting genetic instability in a subset of patients.