Showing papers by "Guy A. Rouleau published in 1990"

Molecular Genetic Analysis of Chromosome 22 in 81 Cases of Meningioma

Abstract: Constitutional and tumor tissue genotypes from 81 unrelated patients with meningioma were compared at 25 polymorphic loci (restriction fragments length alleles) on chromosome 22. Thirty tumors (37%) retained the constitutional genotype along chromosome 22, a finding consistent with no detectable aberrations on chromosome 22 as studied. Forty-two tumors (52%) showed loss of one allele at all informative loci consistent with monosomy 22 in the tumor DNA. The remaining 9 tumors (11%) showed retained constitutional heterozygosity in the tumor DNA at one or more centromeric loci and loss of the heterozygosity at other telomeric loci, which is consistent with variable terminal deletions of one chromosome 22q in the tumor DNA. The localization of breakpoints in these 9 cases with deletions suggests that a meningioma locus is localized distal to myoglobin locus, within 22q12.3-qter. The male cases showed a higher percentage of tumors with no detectable aberrations on chromosome 22, a finding which may suggest that tumors of males have preferentially smaller rearrangements on chromosome 22q than those of females or that the male and female cases with no detected aberrations have another mechanism of oncogenesis. In view of the recent findings on the localization of the neurofibromatosis-2 gene on chromosome 22, the data from case 11 of our series suggests that the meningioma and the neurofibromatosis-2 loci are separate entities.

Flanking markers bracket the neurofibromatosis type 2 (NF2) gene on chromosome 22.

Abstract: Neurofibromatosis 2 or bilateral acoustic neurofibromatosis (NF2) is a severe autosomal dominant disorder characterized by the development of multiple tumors of the nervous system, including meningiomas, gliomas, neurofibromas, ependymomas, and particularly acoustic neuromas Polymorphic DNA markers have revealed frequent loss of one copy of chromosome 22 in the tumor types associated with NF2 Family studies have demonstrated that the primary defect in NF2 is linked to DNA markers on chromosome 22, suggesting that it involves inactivation of a tumor suppressor gene We have employed a combination of multipoint linkage analysis and examination of deletions in primary tumor specimens to precisely map the NF2 locus between flanking polymorphic DNA markers on chromosome 22 The 13-cM region bracketed by these markers corresponds to 13% of the genetic length of the long arm of chromosome 22 and is expected to contain less than 5 x 10(6) bp of DNA The delineation of flanking markers for NF2 should permit accurate presymptomatic and prenatal diagnosis for the disorder and greatly facilitate efforts to isolate the defective gene on the basis of its location

Clonal analysis of human meningiomas and schwannomas.

Abstract: Meningiomas and schwannomas are two of the most common tumors of the human nervous system. To determine whether these tumors arise from a single cell or from multiple cells, we used molecular genetic techniques to study X chromosome inactivation in meningiomas and schwannomas isolated from females including one who had neurofibromatosis type 2. The tumors were also screened for loss of heterozygosity at several loci on chromosome 22 using polymorphic DNA markers. Among nine meningiomas, at least three of which showed loss of alleles on chromosome 22 and five of which retained heterozygosity for the chromosome 22 alleles examined, all nine tumors were monoclonal. Among eight schwannomas, at least seven of which retained heterozygosity for chromosome 22 loci, seven were monoclonal. We conclude that human meningiomas and schwannomas arise from a single cell.

Equal parental origin of chromosome 22 losses in human sporadic meningioma: no evidence for genomic imprinting.

Abstract: Inactivation of tumor suppressor genes can occur either by mutation at the gene locus or by loss of part or all of the chromosome region containing the gene. The latter is most frequently detected by DNA markers as loss of heterozygosity in the tumor tissue. In several reports, the paternal homologue was preferentially retained in embryonal tumors associated with loss of particular chromosomal regions, suggesting genomic imprinting of the corresponding tumor suppressor loci. To explore the generality of these findings and the possible role of genomic imprinting in adult tumors of the nervous system, we have determined the parental origin of chromosome 22 loss in sporadic meningioma. Of nine cases studied, five tumors retained the maternally derived chromosome 22 homologue while four retained the paternally derived chromosome 22. Thus, in contrast to the embryonal tumors, the meningioma locus on chromosome 22 is inactivated by random mutation in sporadic adult meningiomas.