Accumulation of allelic losses on chromosome 10 in human gliomas at recurrence

Abstract

Aims-To elucidate the implications of allelic loss on chromosome 10 in the malignant progression of human gliomas.Methods-Eight microsatellite loci (D10S249, D10S191, D10S210, D10S219, D10S246, D10S222, D10S221, and D10S212) were analysed for chromosomal deletions in histologically benign and malignant, including recurrent, gliomas. Of the 16 original tumours studied (two astrocytomas, nine anaplastic astrocytomas and five glioblastomas), the histological diagnosis at recurrence was anaplastic astrocytoma in six cases and glioblastoma in 10. Genomic DNA was extracted from formalin fixed, paraffin wax embedded sections. Samples of original and recurrent tumours were paired and amplified using PCR. Samples of histologically normal brain served as controls.Results-Of the original tumours, all five glioblastomas, five (56%) of nine anaplastic astrocytomas and none of the astrocytomas demonstrated loss of heterozygosity (LOH) on chromosome 10. Additional LOH was detected in the five cases of anaplastic astrocytoma that progressed to glioblastoma at recurrence. Additional LOH was not detected in the two cases of astrocytoma that progressed to anaplastic astrocytoma at recurrence. With the exception of one case, additional LOH was observed in the recurrent glioblastomas.Conclusion-LOH was observed at the loci of two adjacent microsatellite markers, D10S222 and D10S221 (10q23-q25), suggesting that this region on chromosome 10 is closely related to progression from anaplastic astrocytoma to glioblastoma.