title: Novel fibroblast growth factor receptor 3 (FGFR3) mutations in bladder cancer previously identified in non-lethal skeletal disorders.
abstract: Activating mutations in the fibroblast growth factor receptor 3 (FGFR3) gene are responsible for several autosomal dominant craniosynostosis syndromes and chondrodysplasias i.e. hypochondroplasia, achondroplasia, SADDAN and thanatophoric dysplasia--a neonatal lethal dwarfism syndrome. Recently, activating FGFR3 mutations have also been found to be present in cancer, i.e. at high frequency in carcinoma of the bladder and rarely in multiple myeloma and carcinoma of the cervix. Almost all reported mutations in carcinomas corresponded to the mutations identified in thanatophoric dysplasia. We here screened a series of 297 bladder tumours and found three FGFR3 somatic mutations (G380/382R; K650/652M and K650/652T) that were not previously identified in carcinomas or thanatophoric dysplasia. Another novel finding was the occurrence of two simultaneous FGFR3 mutations in four tumours. Two of the three new mutations in bladder cancer, the G380/382R and the K650/652M mutations, were previously reported in achondroplasia and SADDAN, respectively. These syndromes entail a longer life span than thanatophoric dysplasia. The K650/652T mutation has not previously been detected in patients with skeletal disorders, but affects a codon that has been shown to be affected in some cases of thanatophoric dysplasia, SADDAN and hypochondroplasia. From a clinical perspective, the patients with FGFR3-related, non-lethal skeletal disorders might be at a higher risk for development of bladder tumours than the general population.
authors.affiliation: Department of Pathology, Josephine Nefkens Institute, Erasmus University, 3000 DR Rotterdam, The Netherlands.
authors.forename: Bas W G
authors.initials: BW
authors.lastname: van Rhijn
authors.forename: Angela A G
authors.initials: AA
authors.lastname: van Tilborg
authors.forename: Irene
authors.initials: I
authors.lastname: Lurkin
authors.forename: Jacky
authors.initials: J
authors.lastname: Bonaventure
authors.forename: Annie
authors.initials: A
authors.lastname: de Vries
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Thiery
authors.forename: Theodorus H
authors.initials: TH
authors.lastname: van der Kwast
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Zwarthoff
authors.forename: Francois
authors.initials: F
authors.lastname: Radvanyi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001847:Bone Diseases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D017468:Receptors, Fibroblast Growth Factor; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3