Aneuploidy and improved growth are coincident but not causal in a yeast cancer model

• Published in: PLoS biology Vol. 7; no. 7; p. e1000161
• Main Authors: Li, Xin Chenglin, Schimenti, John C, Tye, Bik K
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28-07-2009; Public Library of Science (PLoS)
• Subjects: Alleles; Analysis; Aneuploidy; Animals; Brewer's yeast; Cancer; Cancer cells; Causes of; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Division; Chromosomes; Development and progression; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; G2 Phase; Gene mutations; Genetic aspects; Genetic testing; Genetics; Genetics and Genomics; Genetics and Genomics/Disease Models; Genomes; Genotype & phenotype; Growth; Mice; Microbiology; Minichromosome Maintenance Complex Component 4; Mutation; Neoplasms, Experimental - genetics; Neoplasms, Experimental - metabolism; Oncology/Breast Cancer; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Yeast; United States; Aneuploidy; Minichromosome Maintenance Complex Component 4; Animals; Cell Division; Alleles; Saccharomyces cerevisiae Proteins; G2 Phase; Neoplasms, Experimental; Mice; Mutation; Saccharomyces cerevisiae; Cell Cycle Proteins; DNA-Binding Proteins
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.1000161

Cancer cells have acquired mutations that alter their growth. Aneuploidy that typify cancer cells are often assumed to contribute to the abnormal growth characteristics. Here we test the idea of a link between aneuploidy and mutations allowing improved growth, using Saccharomyces cerevisiae containing a mcm4 helicase allele that was shown to cause cancer in mice. Yeast bearing this mcm4 allele are prone to undergoing a "hypermutable phase" characterized by a changing karyotype, ultimately yielding progeny with improved growth properties. When such progeny are returned to a normal karyotype by mating, their improved growth remains. Genetic analysis shows their improved growth is due to mutations in just a few loci. In sum, the effects of the mcm4 allele in mice are recapitulated in yeast, and the aneuploidy is not required to maintain improved growth.