title: Roles of FHIT and WWOX fragile genes in cancer.
abstract: It was hypothesized as early as 1986, that the recently discovered common fragile sites could facilitate recombination events, such as deletions and translocations, that result in clonally expanded cancer cell populations with specific chromosome alterations in specific cancer types. A natural extension of this hypothesis is that the clonal expansion must be driven by alteration of genes at recombination breakpoints whose altered functions actually drive clonal expansion. Nevertheless, when the FHIT gene was discovered at FRA3B, the most active common chromosome fragile region, and proposed as an example of a tumor suppressor gene altered by chromosome translocations and deletions, a wave of reports suggested that the FHIT gene was altered in cancer simply because it was in a fragile region and not because it had contributed to the clonal expansion, thus turning the original hypothesis upside down. Now, after nearly ten years and more than 500 FHIT reports, it is apparent that FHIT is an important tumor suppressor gene and that there are genes at other fragile regions that contribute significantly to development of cancer. A second fragile gene with a demonstrated role in cancer development is the WWOX gene on chromosome 16q; alterations to the WWOX gene contribute to development of hormone responsive and other cancers. Results of our recent studies of these two fragile tumor suppressor genes were summarized at the first Fragilome meeting in Heidelberg, Feb. 2005.
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Iliopoulos
authors.forename: Gulnur
authors.initials: G
authors.lastname: Guler
authors.forename: Shuang-Yin
authors.initials: SY
authors.lastname: Han
authors.forename: Teresa
authors.initials: T
authors.lastname: Druck
authors.forename: Michelle
authors.initials: M
authors.lastname: Ottey
authors.forename: Kelly A
authors.initials: KA
authors.lastname: McCorkell
authors.forename: Kay
authors.initials: K
authors.lastname: Huebner
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D043283:Chromosome Fragile Sites / Q000502:physiology*; D002873:Chromosome Fragility; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D044127:Epigenesis, Genetic; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D010088:Oxidoreductases / Q000235:genetics*; D025521:Tumor Suppressor Proteins; D000074584:WW Domain-Containing Oxidoreductase; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D010088:Oxidoreductases; D025521:Tumor Suppressor Proteins; D000074584:WW Domain-Containing Oxidoreductase; D000099170:Bis(5'-adenosyl)triphosphatase; C486071:WWOX protein, human