This paper develops a mathematical model describing the evolutionary dynamics of a unicellular, asexually replicating population exhibiting chromosomal instability. Chromosomal instability is a form of genetic instability characterized by the gain or loss of entire chromosomes during cell division. We assume that the cellular genome is divided into several homologous groups of chromosomes, and ...

We developed mouse model systems to investigate the potential for cyclin D1 to induce CIN in vivo. In a mammary gland specific Tet-inducible model the acute expression profile regulated by cyclin D1 after 7 days was enriched in genes that rank highly with CIN. We also used a mammary gland targeted model (MMTV) to continuously express cyclin D1. The mice started to develop mammary gland tumors a...

To investigate the role of DNA strand breakage as the molecular lesion responsible for initiating genomic instability, five different strand-breaking agents, bleomycin, neocarzinostatin, hydrogen peroxide, restriction endonucleases, and ionizing radiation, were examined for their capacity to induce delayed chromosomal instability. These studies used GM10115 human-hamster hybrid cells, which con...

The link between aneuploidy and cancer has been recognized over a century ago (1). Abnormalities in chromosome copy numbers arise from persistent errors in chromosome segregation during cell division, a process known as chromosomal instability (CIN) (2). CIN is a principal contributor to genetic heterogeneity in cancer (3) and is an important determinant of clinical prognosis and therapeutic re...