FRA3B and other common fragile sites: the weakest links.
In 1979, the first chromosome alteration associated with familial cancer was reported. Five years later, a fragile site was observed in the same chromosome region. The product of the fragile histidine triad (FHIT) gene, which encompasses this fragile site, is partially or entirely lost in most human cancers, indicating that it has a tumour-suppressor function. Inactivation of only one FHIT allele compromises this suppressor function, indicating that a 'one-hit' mechanism of tumorigenesis is operative. Are genes disrupted at other fragile sites? And, are these genes also tumour suppressors?
Huebner
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Kimmel Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA. K_Huebner@lac.jci.tju.edu
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D017766:Acid Anhydride Hydrolases; D000328:Adult; D000483:Alleles; D020816:Amino Acid Motifs; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D019457:Chromosome Breakage; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics* / Q000648:ultrastructure; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics / Q000648:ultrastructure; D017124:Conserved Sequence; D004261:DNA Replication; D004938:Esophageal Neoplasms / Q000235:genetics / Q000517:prevention & control; D005544:Forecasting; D005770:Gastrointestinal Neoplasms / Q000139:chemically induced / Q000235:genetics; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D015316:Genetic Therapy; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011995:Recombination, Genetic; D013329:Structure-Activity Relationship; D014178:Translocation, Genetic; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase