title: Identification of fibroblast growth factor receptor 3 mutations in urine sediment DNA samples complements cytology in bladder tumor detection.
abstract: BACKGROUND
  Mutations in fibroblast growth factor 3 receptor (FGFR3) are frequent events in low-grade bladder tumors. To assess the potential utility of the detection of FGFR3 mutations in a screening modality, the authors analyzed urine sediment DNA samples from 192 patients in a retrospective study.
  
  
  METHODS
  Urine sediment DNA samples from 192 patients were prepared. Seventy-two patients had undergone transurethral resection (TURBT group) of mainly Ta lesions and 120 patients had undergone cystectomy (cystectomy group). The majority of patients in the cystectomy group had more advanced tumors compared with patients in the TURBT group. DNA preparations were screened for FGFR3 mutations in exons 7, 10, and 15 using single-strand conformation polymorphism (SSCP) and DNA sequencing.
  
  
  RESULTS
  Using SSCP, 67% of patients in the TURBT group and 28% in the cystectomy group displayed FGFR3 mutations. Comparative analysis of cytology results and FGFR3 mutational analysis were performed in 122 cases. Within the TURBT group, FGFR3 mutation analysis outperformed cytology. FGFR3 mutation analysis identified change in 68% of urine sediment DNA samples whereas cytology recorded the presence of tumor cells in 32% of the DNA samples. In the cystectomy group, cytology outperformed FGFR3 mutation analysis. Cytology recorded tumor detection in 90% of patients, while SSCP identified mutational change in 24%.
  
  
  CONCLUSIONS
  Combining FGFR3 mutation results with cytology in both groups correctly identified tumor presence in 105 of 122 (86%) of patients. The greater sensitivity of FGFR3 mutation detection over cytology in identifying the presence of low-grade, superficial bladder tumors represents a potential new tool to complement standard cytology in screening patients for bladder tumors and recurrent disease.
authors.affiliation: Cell and Molecular Biology Laboratory, Robert E. Wise M. D. Research and Education Institute, Burlington, Massachusetts, USA.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Rieger-Christ
authors.forename: Arthur
authors.initials: A
authors.lastname: Mourtzinos
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lee
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Zagha
authors.forename: Jason
authors.initials: J
authors.lastname: Cain
authors.forename: Mark
authors.initials: M
authors.lastname: Silverman
authors.forename: John A
authors.initials: JA
authors.lastname: Libertino
authors.forename: Ian C
authors.initials: IC
authors.lastname: Summerhayes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003581:Cytodiagnosis; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000652:urine*; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018807:Polymorphism, Single-Stranded Conformational; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery
chemical_list: D004273:DNA, Neoplasm; D017468:Receptors, Fibroblast Growth Factor; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3