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Title: Mitotic recombination of chromosome 17 in astrocytomas

Abstract

Allelic combinations at seven loci on human chromosome 17 defined by restriction fragment length polymorphisms were determined in tumor and normal tissues from 35 patients with gliomas. Loss of constitutional heterozygosity at one or more of these loci was observed in 8 of the 24 tumors displaying astrocytic differentiation and in the single primitive neuroectodermal tumor examined. The astrocytomas showing these losses included examples of each adult malignancy grade of the disease, including glioblastoma (malignancy grade IV), and seven of them demonstrated concurrent maintenance of heterozygosity for at least one chromosome 17 locus. Determination of allele dosage together with the genotypic data indicated that the tumor chromosomes 17 were derived by mitotic recombination in 7 of the 9 cases with shared homozygosity of the region 17p11.2-ptr in all cases. In contrast, tumors of oligodendrocytic, ependymal, or mixed cellular differentiation did not exhibit loss of alleles at any of the loci examined. These data suggest that the somatic attainment of homozygosity for loci on chromosome 17p is frequently associated with the oncogenesis of central nervous system tumors, particularly those showing solely astrocytic differentiation, and that mitotic recombination mapping is a useful approach towards the subregional localization of a locus whose rearrangementmore » is involved in this disease.« less

Authors:
; ; ; ;  [1]
  1. (Ludwig Institute for Cancer Research, Montreal (Canada))
Publication Date:
OSTI Identifier:
5263170
Resource Type:
Journal Article
Resource Relation:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA); Journal Volume: 86:8
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ASTROCYTOMAS; GENETICS; DNA; AUTORADIOGRAPHY; HETEROCHROMOSOMES; GENE RECOMBINATION; CHROMOSOMAL ABERRATIONS; MAN; RFLPS; ANIMALS; BIOLOGY; CHROMOSOMES; DISEASES; GLIOMAS; MAMMALS; MUTATIONS; NEOPLASMS; NUCLEIC ACIDS; ORGANIC COMPOUNDS; PRIMATES; VERTEBRATES; 550401* - Genetics- Tracer Techniques

Citation Formats

James, C.D., Carlbom, E., Nordenskjold, M., Collins, V.P., and Cavenee, W.K. Mitotic recombination of chromosome 17 in astrocytomas. United States: N. p., 1989. Web. doi:10.1073/pnas.86.8.2858.
James, C.D., Carlbom, E., Nordenskjold, M., Collins, V.P., & Cavenee, W.K. Mitotic recombination of chromosome 17 in astrocytomas. United States. doi:10.1073/pnas.86.8.2858.
James, C.D., Carlbom, E., Nordenskjold, M., Collins, V.P., and Cavenee, W.K. 1989. "Mitotic recombination of chromosome 17 in astrocytomas". United States. doi:10.1073/pnas.86.8.2858.
@article{osti_5263170,
title = {Mitotic recombination of chromosome 17 in astrocytomas},
author = {James, C.D. and Carlbom, E. and Nordenskjold, M. and Collins, V.P. and Cavenee, W.K.},
abstractNote = {Allelic combinations at seven loci on human chromosome 17 defined by restriction fragment length polymorphisms were determined in tumor and normal tissues from 35 patients with gliomas. Loss of constitutional heterozygosity at one or more of these loci was observed in 8 of the 24 tumors displaying astrocytic differentiation and in the single primitive neuroectodermal tumor examined. The astrocytomas showing these losses included examples of each adult malignancy grade of the disease, including glioblastoma (malignancy grade IV), and seven of them demonstrated concurrent maintenance of heterozygosity for at least one chromosome 17 locus. Determination of allele dosage together with the genotypic data indicated that the tumor chromosomes 17 were derived by mitotic recombination in 7 of the 9 cases with shared homozygosity of the region 17p11.2-ptr in all cases. In contrast, tumors of oligodendrocytic, ependymal, or mixed cellular differentiation did not exhibit loss of alleles at any of the loci examined. These data suggest that the somatic attainment of homozygosity for loci on chromosome 17p is frequently associated with the oncogenesis of central nervous system tumors, particularly those showing solely astrocytic differentiation, and that mitotic recombination mapping is a useful approach towards the subregional localization of a locus whose rearrangement is involved in this disease.},
doi = {10.1073/pnas.86.8.2858},
journal = {Proceedings of the National Academy of Sciences of the United States of America; (USA)},
number = ,
volume = 86:8,
place = {United States},
year = 1989,
month = 4
}
  • The results of recent genetic and cytological studies on recombination-defective and repair-defective mutants of Drosophila melanogaster are summarized. These studies show that there is substantial overlap between the functions used in various aspects of DNA metabolism in Drosophila. Most loci first identified by either recombination-defective or mutagen-sensitive mutants have been shown also to function in nonmutagenized mitotic cells where their action is necessary to maintain the integrity of the genome: mutants at particular loci produce elevated frequencies of chromosome breakage, mitotic exchange, mutation, and/or chromosome loss. Genetic studies of meiotic recombination show that many of the loci identified by recombination-defectivemore » mutants restrict where along the chromosome arms exchange may occur. Recent EM studies suggest that the products of at least some of these loci are components of recombination nodules. Region-specific control of DNA metabolism is also indicated by the finding of nonrandom patterns of chromosome breakage in some mutagen-sensitive mutants. Recombination-defective mutants at two loci have been studied for their effects on sister chromatid exchanges and x-ray induced aberrations. Mutants at both loci are defective in steps necessary for the production of symmetrical chromatid interchanges but have little effect on SCEs.« less
  • Somatic cell hybrids heterozygous at the emetine resistance locus (emt/sup r//emt/sup +/) or the chromate resistance locus (chr/sup r//chr/sup +/) are known to segregate the recessive drug resistance phenotype at high frequency. The authors have examined mechanisms of segregation in Chinese hamster cell hybrids heterozygous at these two loci, both of which map to the long arm of Chinese hamster chromosome 2. To allow the fate of chromosomal arms through the segregation process, our hybrids were also heterozygous at the mtx (methotrexate resistance) locus on the short arm of chromosome 2 and carried cytogenetically marked chromosomes with either a short-armmore » deletion 2p/sup -/) or a long-arm addition (2q/sup +/). Karotype and phenotype analysis of emetine- or chromate-resistant segregants from such hybrids allowed us to distinguish four potential segregation mechanisms: (i) loss of the emt/sup +/ - or chr/sup +/-bearing chromosome; (ii) mitotic recombination between the centromere and the emt or chr loci giving rise to homozygous resistant segregants; (iii) inactivation of the emt/sup +/ or chr/sup +/ alleles; and (iv) loss of the emt/sup +/ - or chr/sup +/-bearing chromosome with duplication of the homologous chromosome carrying the emt/sup r/ or chr/sup r/ allele. Of 48 independent segregants examined, only 9 (20%) arose by simple chromosome loss. Two segregants (4%) were consistent with a gene inactivation mechanism, but because of their rarity, other mechanisms such as mutation or submicroscopic deletion could not be excluded. Twenty-one segregants (44%) arose by either mitotic recombination or chromosome loss and duplication; the two mechanisms were not distinguishable in that experiment. Finally, in hybrids allowing these two mechanisms to be distinguished, 15 segregants (31%) arose by chromosome loss and duplication, and none arose by mitotic recombination.« less
  • Semi-dominant mutants displaying greatly elevated levels of spontaneous mitotic recombination have been isolated in a disomic haploid strain of yeast heteroallelic at the arg4 locus. They are designated by the symbol MIC. The mutants variously exhibit associated sensitivity to uv and ionizing radiation and to methyl methanesulfonate, enhanced uv-induced mitotic recombiation, and enhanced spontaneous forward mutation rates. Possible enzyme defects and involvement in repair and editing of DNA are discussed. The mutants are expected to simplify the analysis of recombination pathways in yeast.