ACCUMULATION OF ALLELIC LOSSES ON CHROMOSOME-10 IN HUMAN GLIOMAS AT RECURRENCE

Aims-To elucidate the implications of allelic loss on chromosome 10 in the malignant progression of human gliomas. Methods-Eight microsatell ite loci (D10S249, D10S191, D10S210, D10S219, D10S246, D10S222, D10S22 1, and D10S212) were analysed for chromosomal deletions in histologica lly benign and malignant, including recurrent, gliomas. Of the 16 orig inal tumours studied (two astrocytomas, nine anaplastic astrocytomas a nd five glioblastomas), the histological diagnosis at recurrence was a naplastic astrocytoma in six cases and glioblastoma in 10. Genomic DNA was extracted from formalin fixed, paraffin wax embedded sections. Sa mples of original and recurrent tumours were paired and amplified usin g PCR. Samples of histologically normal brain served as controls. Resu lts-Of the original tumours, all five glioblastomas, five (56%) of nin e anaplastic astrocytomas and none of the astrocytomas demonstrated lo ss of heterozygosity (LOH) on chromosome 10. Additional LOH was detect ed in the five cases of anaplastic astrocytoma that progressed to glio blastoma at recurrence. Additional LOH was not detected in the two cas es of astrocytoma that progressed to anaplastic astrocytoma at recurre nce. With the exception of one case, additional LOH was observed in th e 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 pro gression from anaplastic astrocytoma to glioblastoma.