The incidence of thanatophoric dysplasia mutations in FGFR3 gene is higher in low-grade or superficial bladder carcinomas

Cancer. 2001 Nov 15;92(10):2555-61. doi: 10.1002/1097-0142(20011115)92:10<2555::aid-cncr1607>3.0.co;2-m.

Abstract

Background: The point mutations of fibroblast growth factor receptor 3 (FGFR3) are associated with autosomal dominant human skeletal disorders such as thanatophoric dysplasia (TD). However, point mutations were reported in a small series of bladder carcinomas, suggesting their oncogenic role. In view of these findings, the authors investigated the incidence of TD mutations in the FGFR3 gene in a large series of bladder carcinomas to clarify their role in the progression of bladder carcinoma.

Methods: Specimens of transitional cell carcinoma of the urinary bladder from 81 patients were screened for the FGFR3 mutations (codons 248, 249, 372, 373, 375, 652, 809) that have been reported in TD, using polymerase chain reaction-restriction fragment length polymorphism, single-strand conformation polymorphism, and DNA sequencing.

Results: Point mutations were detected in 25 of 81 carcinomas (2 at codon 248, 11 at codon 249, 1 at codon 372, 9 at codon 375, 2 at codon 652). Although no significant relation was found between the occurrence of TD mutations and patient age and clinical status, the incidence of TD mutations was significantly higher in low-grade or superficial tumors than high-grade or muscle invasive tumors.

Conclusions: These findings indicate that TD mutations in the FGFR3 gene do not cause disease progression of bladder carcinoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Transitional Cell / genetics*
  • Cell Transformation, Neoplastic
  • Disease Progression
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Point Mutation*
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single-Stranded Conformational
  • Protein-Tyrosine Kinases*
  • Receptor, Fibroblast Growth Factor, Type 3
  • Receptors, Fibroblast Growth Factor / genetics*
  • Sequence Analysis, DNA
  • Thanatophoric Dysplasia / genetics*
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology*

Substances

  • Receptors, Fibroblast Growth Factor
  • FGFR3 protein, human
  • Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 3