title: Chromosome instability, chromosome transcriptome, and clonal evolution of tumor cell populations.
abstract: Chromosome instability and aneuploidy are hallmarks of cancer, but it is not clear how changes in the chromosomal content of a cell contribute to the malignant phenotype. Previously we have shown that we can readily isolate highly proliferative tumor cells and their revertants from highly invasive tumor cell populations, indicating how phenotypic shifting can contribute to malignant progression. Here we show that chromosome instability and changes in chromosome content occur with phenotypic switching. Further, we show that changes in the copy number of each chromosome quantitatively impose a proportional change in the chromosome transcriptome ratio. This correlation also applies to subchromosomal regions of derivative chromosomes. Importantly, we show that the changes in chromosome content and the transcriptome favor the expression of a large number of genes appropriate for the specific tumor phenotype. We conclude that chromosome instability generates the necessary chromosome diversity in the tumor cell populations and, therefore, the transcriptome diversity to allow for environment-facilitated clonal expansion and clonal evolution of tumor cell populations.
authors.affiliation: Laboratory of Molecular Oncology, Van Andel Research Institute, 333 Bostwick Avenue, N.E., Grand Rapids, MI 49503, USA.
authors.forename: ChongFeng
authors.initials: C
authors.lastname: Gao
authors.forename: Kyle
authors.initials: K
authors.lastname: Furge
authors.forename: Julie
authors.initials: J
authors.lastname: Koeman
authors.forename: Karl
authors.initials: K
authors.lastname: Dykema
authors.forename: Yanli
authors.initials: Y
authors.lastname: Su
authors.forename: Mary Lou
authors.initials: ML
authors.lastname: Cutler
authors.forename: Adam
authors.initials: A
authors.lastname: Werts
authors.forename: Pete
authors.initials: P
authors.lastname: Haak
authors.forename: George F
authors.initials: GF
authors.lastname: Vande Woude
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D043171:Chromosomal Instability / Q000235:genetics*; D002877:Chromosomes, Human / Q000235:genetics*; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D014158:Transcription, Genetic / Q000235:genetics*; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism
chemical_list: D014568:Urokinase-Type Plasminogen Activator