Low frequency of replication errors in primary nervous system tumours

Abstract

OBJECTIVES Automated DNA technology was used to analyze the incidence of microsatellite instability (MIN) among the most frequent types of adult primary CNS tumours and to determine its relation with clinicopathological characteristics. METHODS Fifty six gliomas, 32 meningiomas and 11 schwannomas were screened for size changes at eight microsatellite loci using fluorescent polymerase chain reaction (PCR) followed by fragment analysis in an automated sequencer. A tumour was considered as MIN+ when a different electrophoretic pattern between constitutional and tumour DNA was evidenced in one or more microsatellite markers and as replication error positive (RER+) when at least 25% of the markers analyzed (2/8) showed instability. The MIN phenotype was correlated with relevant clinical and pathological parameters. RESULTS Globally, instability was found in 19/767 analyses (2.47%), with a higher rate among tetranuceotide than dinucleotide repeats (χ² test, p=0.018). Ten gliomas (17.9%), two meningiomas (6.3%), and two schwannomas (18.2%) were MIN+, whereas one glioma (1.8%), two meningiomas (6.3%), and one schwannoma (9.1%) were classified as RER+. A possible association between microsatellite instability and a shorter duration of clinical course was found in meningiomas. The MIN+ phenotype was more frequent in spinal than intracranial schwannomas (Fisher's exact test, p=0.018). No other significant association with clinical or histological features was detected. CONCLUSIONS Although microsatellite instability can be demonstrated at a low rate in some primary CNS tumours, a true replication error phenotype (revealed by widespread microsatellite instability at numerous loci) is uncommon and unlikely to play an important part in the pathogenesis of these neoplasms. This form of instability was more frequent in tetranucleotide than in dinucleotide repeats. To our knowledge, this is the first report of MIN in schwannomas, where it was associated with the spinal localisation of the tumour.