Marked aneuploidy and loss of multiple chromosomes are hallmarks of cancer, but whether these events are only present in malignant cells is not known. In prior work, we showed that approximately half of spontaneous autosomal mutants isolated directly from normal kidney epithelium arose from loss of a marker chromosome 8 containing the wild type Aprt gene. Chromosome loss was detected by loss of heterozygosity (LOH) for all chromosome 8 polymorphic loci examined (Turker et al, Aging Cell, 6:73-86, 2007). To determine whether loss of chromosome 8 reflected a larger mitotic event, LOH was examined for polymorphic loci on 11 non-selected chromosomes in Aprt mutants that lost the selected chromosome 8 homologue. LOH events were detected for one or more non-selected chromosomes in 38% of these mutants. The additional LOH events also reflected apparent chromosome loss based on the molecular analysis. Metaphase spreads from mutants that lost chromosome 8 were markedly aneuploid and chromosome painting revealed reduced levels for any chromosome shown to be lost with the LOH analysis. In contrast, LOH on non-selected chromosomes was infrequent in Aprt mutants exhibiting intragenic events or mitotic recombination for chromosome 8, and marked aneuploidy was absent. These observations suggest that the mechanism leading to chromosome loss in somatic mammalian cells is often not a simple non-disjunction event and instead could result from a single catastrophic event. They also suggest that cells with characteristics of malignancy are present in normal appearing tissue.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.