title: Chromosome instability in cancer: how, when, and why?
abstract: The majority of malignant tumors exhibit complex genomic aberrations, and it has been suggested that an elevated rate of chromosome mutation is present in neoplastic cells. This chromosomal evolution is probably initiated at a preinvase stage and then proceeds continuously but at variable rates during tumor progression. Even though the initiating events may vary among neoplasms, the end point is often a similar set of cytogenetic and cytological events. These include an excessive shortening of telomeric repeats, disrupting the normal mitotic process and triggering chromosomal breakage-fusion-bridge events and gross genomic imbalances. Telomere dysfunction may also cause a failure of cytokinesis, resulting in tetraploidization and the accumulation of supernumerary centrosomes. In turn, this could cause multipolar cell division and gross aberrations in chromosome number. Several well-known cancer risk factors could contribute to these processes. For instance, breakage-fusion-bridge instability can be induced directly by clastogenic substances, whereas papilloma virus infection has been shown to dysregulate centrosome function. A prerequisite for the induction of chromosome instability through these mechanisms is partial inactivation of the DNA damage response and the mitotic checkpoint functions. Also, overexpression of telomerase appears to play a crucial role for moderating the rate of chromosomal evolution.
authors.affiliation: Department of Clinical Genetics, University Hospital SE-221 85 Lund, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Gisselsson
mesh_terms: D002869:Chromosome Aberrations; D005826:Genetics, Medical / Q000379:methods / Q000639:trends; D015894:Genome, Human; D006570:Heterochromatin / Q000235:genetics; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000145:classification / Q000235:genetics*
chemical_list: D006570:Heterochromatin