Mechanisms of Chromosomal Instability

Mechanisms of Chromosomal Instability

Most solid tumors are aneuploid, having a chromosome number that is not a multiple of the haploid number, and many frequently mis-segregate whole chromosomes in a phenomenon called chromosomal instability (CIN). CIN positively correlates with poor patient prognosis, indicating that reduced mitotic fidelity contributes to cancer progression by increasing genetic diversity among tumor cells. Here...

Mouse Models for Chromosomal Instability

Chromosomal instability and human cancer.

Genetic instability is a defining feature of human cancer. The main type of genetic instability, chromosomal instability (CIN), enhances the rate of gross chromosomal changes during cell division. CIN is brought about by mutations of CIN genes, i.e. genes that are involved in maintaining the genomic integrity of the cell. A major question in cancer genetics is whether genetic instability is a c...

Cyclin D1 Induces Chromosomal Instability

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...

Chromosomal Instability, Aneuploidy, and Cancer

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...