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.
Popescu
Nicholas C
NC
Molecular Cytogenetics Section, Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20814-4958, USA. popescum@dc37a.nci.nih.gov
D002273:Carcinogens / Q000494:pharmacology; D019457:Chromosome Breakage / Q000235:genetics*; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009153:Mutagens / Q000494:pharmacology; D009369:Neoplasms / Q000139:chemically induced / Q000209:etiology / Q000235:genetics* / Q000821:virology; D011995:Recombination, Genetic / Q000187:drug effects / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics
D002273:Carcinogens; D009153:Mutagens