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 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.

[1]  M Koslow,et al.  Pathways leading to glioblastoma multiforme: a molecular analysis of genetic alterations in 65 astrocytic tumors. , 1994, Journal of neurosurgery.

[2]  J. Rey,et al.  Molecular analysis of genomic abnormalities in human gliomas. , 1994, Cancer genetics and cytogenetics.

[3]  P. Black,et al.  Genetic Aberrations in Human Brain Tumors , 1994 .

[4]  E Stubblefield,et al.  Analysis of the functional role of chromosome 10 loss in human glioblastomas. , 1993, Cancer research.

[5]  D. Louis,et al.  Subsets of Glioblastoma Multiforme Defined by Molecular Genetic Analysis , 1993, Brain pathology.

[6]  P. Kelly,et al.  Correlation of cytogenetic analysis and loss of heterozygosity studies in human diffuse astrocytomas and mixed oligo‐astrocytomas , 1992, Genes, Chromosomes and Cancer.

[7]  G. Gyapay,et al.  A second-generation linkage map of the human genome , 1992, Nature.

[8]  A. Friedman,et al.  Loss of heterozygosity for 10q loci in human gliomas , 1992, Genes, chromosomes & cancer.

[9]  D. Smailus,et al.  Human repeat element-mediated PCR: cloning and mapping of chromosome 10 DNA markers. , 1992, Genomics.

[10]  C. James,et al.  Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N- and/or C-terminal tails. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[11]  I. Petersen,et al.  p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma. , 1992, Cancer research.

[12]  E. Newcomb,et al.  p53 mutations in human malignant gliomas: comparison of loss of heterozygosity with mutation frequency. , 1992, Cancer research.

[13]  M. Santoro,et al.  Characterization of an inversion on the long arm of chromosome 10 juxtaposing D10S170 and RET and creating the oncogenic sequence RET/PTC. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[14]  R. Cawthon,et al.  p53 mutation and loss of heterozygosity on chromosomes 17 and 10 during human astrocytoma progression. , 1992, Cancer research.

[15]  R. Martuza,et al.  TP53 Gene Mutations and 17p Deletions in Human Astrocytomas , 1991, Genes, chromosomes & cancer.

[16]  S. Leon,et al.  Genetic aberrations in human brain tumors. , 1994, Neurosurgery.

[17]  B. Darras,et al.  Loss of heterozygosity for alleles on chromosome 10 in human brain tumours. , 1993, Neurological research.