title: FGFR3 and TP53 gene mutations define two distinct pathways in urothelial cell carcinoma of the bladder.
abstract: FGFR3 and TP53 mutations are frequent in superficial papillary and invasive disease, respectively. We used denaturing high-performance liquid chromatography and sequencing to screen for FGFR3 and TP53 mutations in 81 newly diagnosed urothelial cell carcinomas. Tumors were classified as follows: 31 pTa, 1 carcinoma in situ, 30 pT1, and 19 pT2-T4. Tumor grades were as follows: 10 G1, 29 G2, and 42 G3. FGFR3 mutations were associated with low-stage (P < 0.0001), low-grade (P < 0.008) tumors, whereas TP53 mutations were associated with high-stage (P < 0.003), high-grade (P < 0.02) tumors. Mutations in these two genes were almost mutually exclusive. Our results suggest that FGFR3 and TP53 mutations define separate pathways at initial diagnosis of urothelial cell carcinoma.
authors.affiliation: Equipe mixte Inserm Institut National de la Santé et de la Recherche Médicale, and Service d'Urologie, Paris, France.
authors.forename: Ashraf A
authors.initials: AA
authors.lastname: Bakkar
authors.forename: Herve
authors.initials: H
authors.lastname: Wallerand
authors.forename: François
authors.initials: F
authors.lastname: Radvanyi
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Lahaye
authors.forename: Serge
authors.initials: S
authors.lastname: Pissard
authors.forename: Laure
authors.initials: L
authors.lastname: Lecerf
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Kouyoumdjian
authors.forename: Claude C
authors.initials: CC
authors.lastname: Abbou
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Pairon
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Jaurand
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Thiery
authors.forename: Dominique K
authors.initials: DK
authors.lastname: Chopin
authors.forename: Sixtina Gil Diez
authors.initials: SG
authors.lastname: de Medina
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; 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