title: Frequent FGFR3 mutations in papillary non-invasive bladder (pTa) tumors.
abstract: We recently identified activating mutations of fibroblast growth factor receptor 3 (FGFR3) in bladder carcinoma. In this study we assessed the incidence of FGFR3 mutations in a series of 132 bladder carcinomas: 20 carcinoma in situ (CIS), 50 pTa, 19 pT1, and 43 pT2-4. All 48 mutations identified were identical to the germinal activating mutations that cause thanatophoric dysplasia, a lethal form of dwarfism. The S249C mutation, found in 33 of the 48 mutated tumors, was the most common. The frequency of mutations was higher in pTa tumors (37 of 50, 74%) than in CIS (0 of 20, 0%; P < 0.0001), pT1 (4 of 19, 21%; P < 0.0001) and pT2-4 tumors (7 of 43, 16%; P < 0.0001). FGFR3 mutations were detected in 27 of 32 (84%) G1, 16 of 29 (55%) G2, and 5 of 71 (7%) G3 tumors. This association between FGFR3 mutations and low grade was highly significant (P < 0.0001). FGFR3 is the first gene found to be mutated at a high frequency in pTa tumors. The absence of FGFR3 mutations in CIS and the low frequency of FGFR3 mutations in pT1 and pT2-4 tumors are consistent with the model of bladder tumor progression in which the most common precursor of pT1 and pT2-4 tumors is CIS.
authors.affiliation: Service d'Anatomie et de Cytologie Pathologiques, Centre Hospitalo-Universitaire de Rouen, Hôpital Charles Nicolle, Rouen, France.
authors.forename: C
authors.initials: C
authors.lastname: Billerey
authors.forename: D
authors.initials: D
authors.lastname: Chopin
authors.forename: M H
authors.initials: MH
authors.lastname: Aubriot-Lorton
authors.forename: D
authors.initials: D
authors.lastname: Ricol
authors.forename: S
authors.initials: S
authors.lastname: Gil Diez de Medina
authors.forename: B
authors.initials: B
authors.lastname: Van Rhijn
authors.forename: M P
authors.initials: MP
authors.lastname: Bralet
authors.forename: M A
authors.initials: MA
authors.lastname: Lefrere-Belda
authors.forename: J B
authors.initials: JB
authors.lastname: Lahaye
authors.forename: C C
authors.initials: CC
authors.lastname: Abbou
authors.forename: J
authors.initials: J
authors.lastname: Bonaventure
authors.forename: E S
authors.initials: ES
authors.lastname: Zafrani
authors.forename: T
authors.initials: T
authors.lastname: van der Kwast
authors.forename: J P
authors.initials: JP
authors.lastname: Thiery
authors.forename: F
authors.initials: F
authors.lastname: Radvanyi
mesh_terms: D002278:Carcinoma in Situ / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017354:Point Mutation; 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