XXXX and loss of multiple chromosomes are common in autosomal mutants isolated from normal mouse kidney epithelium.

@entity1 @entity2007 @entity30179 @entity5 @entity393
@entity2007 and loss of multiple chromosomes are hallmarks of @entity5 , 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 @entity30179 gene. Chromosome loss was detected by loss of heterozygosity (LOH) for all chromosome 8 polymorphic loci examined. To determine whether @entity393 reflected a larger mitotic event, LOH was examined for polymorphic loci on 11 nonselected chromosomes in @entity30179 mutants that lost the selected chromosome 8 homologue. LOH events were detected for one or more nonselected 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 nonselected chromosomes was infrequent in @entity30179 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 @entity1 cells is often not a simple nondisjunction event and instead could result from a single catastrophic event. They also suggest that cells with characteristics of @entity5 are present in normal appearing tissue.
