Chromosomal Instability (CIN) in Cancer

Chris Schmutte, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

Published online: January 2006

DOI: 10.1038/npg.els.0006069

Chromosomal instability is definied as an increased rate of gross chromosomal abnormalities combined with loss of heterozygosity and change in ploidy of genes structural CIN, and the inability of cells to maintain a diploid karyotype numerical CIN.

Keywords: chromosome instability; cancer; selection; Darwinian evolution, microsatelite instability

Figure 1. Comparison of microsatellite instability (MSI) and chromosome instability (CIN) pathways. Flashes indicate assault of DNA-causing damage which is symbolized by vertical arrows (down to ‘Selection’). (a) MMR +/– indicates a heterozyg ous mutation in genes involved in DNA mismatch repair (MMR). MMR inactivation (MMR –/–) causes additional DNA damage, because replication errors are not repaired by MMR. (b) NER +/– represents a heterozygous mutation in DNA nucleotide excision repair (NER) genes. Nonhomologous end-joining (NHEJ) and homologous recombination repair (HHR) are pathways that repair double-strand breaks. HHR can function as a backup repair system for NER when bulky DNA lesions stall the replication fork. Overload of these pathways could lead to inactivation of ‘chromosome stability’ pathways, causing CIN. Asterisk represents partial conversion of the damage to DSB replication and faulty repair by NHEJ and/or HHR.
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 Web Links
    ePath BRCA2(breast cancer 2, early onset); Locus ID: 675. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=675
    ePath BUB1 (BUB1 budding uninhibited by benzimidazoles 1 homolog (yeast)); Locus ID: 699. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=699
    ePath BRCA2 (breast cancer 2, early onset); MIM number: 600185. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600185
    ePath BUB1 (BUB1 budding uninhibited by benzimidazoles 1 homolog (yeast)); MIM number: 602452. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?602452

Related Sub-Topics:

Mutational Mechanisms of Genetic Disease | Cancer Genetics | Gene and Genome Structure and Organisation | Chromosomes and Chromatin Modifications | DNA Damage and Repair
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Article Title: Chromosomal Instability (CIN) in Cancer
 
How to Cite close
Schmutte, Chris(Jan 2006) Chromosomal Instability (CIN) in Cancer. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0006069]