Genetic alterations in cancer as a result of breakage at fragile sites

The organization and replication of DNA render fragile sites (FSs) prone to breakage, recombination as well as becoming preferential targets for mutagens–carcinogens and integration of oncogenic viruses. For many years, attempts to link FSs and cancer generated mostly circumstantial evidence. The discoveries that chromosome translocations, amplification of proto-oncogenes, deletion of tumor suppressor genes, and integration of oncogenic viruses all result from the specific breakage of genomic DNA at FSs, however, have provided compelling support for such a link, further suggesting a causative role for FSs in cancer.