Instability of short tandem repeats (microsatellites) in human gliomas.
OBJECTIVE
Microsatellite instability implying multiple replication errors (RER) characterizes a proportion of familial and sporadic carcinomas. The purpose of this report is to analyze whether microsatellite instability occurred during the development of human gliomas.


METHODS
We checked prospectively 16 central nervous system tumors, including 10 glioblastomas and 6 astrocytomas of different malignancy grades, for genetic microsatellite instability. Fifteen different microsatellites, located on 6 different chromosomes, were investigated. All microsatellites are dinucleotide CA, repeats except for D11S956,P23 (CTAT) and CYP 19, which are tetranucleotide repeats and P23 (GTTTT) which is a pentanucleotide repeat. The repeats were analysed by PCR amplification, followed by electrophoresis on denaturing 6% polyacrylamide gels.


METHODS
We looked for all kinds of microsatellite alterations. Only microsatellite shifts were considered to represent microsatellite instability.


RESULTS
Three out of 10 glioblastomas showed mobility shifts on gel electrophoresis in tumor, compared to corresponding normal DNA samples. In contrast, no microsatellite instability was found in any of the astrocytomas. Besides the presence of larger or smaller alleles, an imbalance in the ratio between alleles was noticed in one astrocytoma and in one glioblastoma multiforme. In addition, loss of heterozygosity (LOH) is observed without a fixed pattern in 3 glioblastomas.


CONCLUSIONS
We conclude that genetic instability of microsatellites may be demonstrated in high grade gliomas rather than in their low grade precursors and should be regarded as an evolution in tumor progression rather than as a new mechanism for tumor initiation in gliomas.
van de Kelft
E
E
Department of Nerurosurgery, Antwerp University Hospital, Belgium.
Verlooy
J
J
D001254:Astrocytoma / Q000235:genetics*; D001483:Base Sequence; D016543:Central Nervous System Neoplasms / Q000235:genetics*; D004261:DNA Replication; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D011446:Prospective Studies