Common Fragile Site Tumor Suppressor Genes and Corresponding Mouse Models of Cancer

Abstract

Chromosomal common fragile sites (CFSs) are specific mammalian genomic regions that show an increased frequency of gaps and breaks when cells are exposed to replication stressin vitro. CFSs are also consistently involved in chromosomal abnormalitiesin vivorelated to cancer. Interestingly, several CFSs contain one or more tumor suppressor genes whose structure and function are often affected by chromosomal fragility. The two most active fragile sites in the human genome are FRA3B and FRA16D where the tumor suppressor genesFHITandWWOXare located, respectively. The best approach to study tumorigenic effects of altered tumor suppressors located at CFSsin vivois to generate mouse models in which these genes are inactivated. This paper summarizes our present knowledge on mouse models of cancer generated by knocking out tumor suppressors of CFS.