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common fragile sites

Tuesday 26 June 2007

Common fragile sites (CFS) are nonstaining gaps or breaks in chromosomes that are expressed under conditions inducing replicative stress.

Common fragile sites (CFSs) are regions of chromosomal break that may play a role in oncogenesis. The most frequent alteration occurs at FRA3B, within the FHIT gene, at chromosomal region 3p14.

Common fragile sites represent a component of normal chromosome structure that form gaps and breaks on metaphase chromosomes after partial inhibition of DNA synthesis.

In humans, cytogenetic locations of 89 common fragile sites are listed in the Genome Database. However, the exact number of fragile sites remains unknown. The application of high resolution mapping approaches continues to reveal new common fragile sites in the human genome.

Pathology

The molecular basis of the fragility of common fragile sites (CFS) and their role in chromosome instability and in altered expression of associated genes in cancer cells have not yet been clarified.

CFS have been suggested to play a role in epithelial cancers by their association with loss of heterozygosity, loss of gene expression, and/or gene amplification in the form of homogeneously staining regions (hsrs).

Examples

- FRA1H is the first characterized CFS the expression of which is not induced by aphidicolin but instead by DAPI. 5-azaC, 5-azadC, and Ad12 induce a CFS with the same cytogenetic location.

- FRA3B, within the FHIT gene, at 3p14.

See also

- Oncobase