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Novel fibroblast growth factor receptor 3 (FGFR3) mutations in bladder cancer previously identified in non-lethal
Bas W G van Rhijn1, Angela A G van Tilborg, Irene Lurkin
1Department of Pathology, Josephine Nefkens Institute, Erasmus University, 3000 DR Rotterdam, The Netherlands.
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.
Insights
Activating fibroblast growth factor receptor 3 (FGFR3) mutations are linked to skeletal disorders and bladder cancer. This study identified novel FGFR3 mutations in bladder tumors, suggesting a potential increased risk for bladder cancer in patients with FGFR3-related skeletal conditions.
Area of Science:
- Genetics
- Oncology
- Skeletal Dysplasias
Background:
- Activating mutations in the fibroblast growth factor receptor 3 (FGFR3) gene are associated with various skeletal dysplasias, including achondroplasia and thanatophoric dysplasia.
- FGFR3 mutations have also been identified in several cancers, notably bladder carcinoma.
Purpose of the Study:
- To investigate the spectrum of FGFR3 mutations in bladder tumors.
- To identify novel FGFR3 mutations in bladder cancer.
- To explore the clinical implications of FGFR3 mutations in skeletal disorders concerning bladder cancer risk.
Main Methods:
- Screening of 297 bladder tumors for FGFR3 somatic mutations.
- Analysis of mutation types and their correlation with skeletal dysplasia syndromes.
Main Results:
- Three novel FGFR3 somatic mutations (G380/382R; K650/652M; K650/652T) were identified in bladder tumors, distinct from those previously found in carcinomas or thanatophoric dysplasia.
- Four bladder tumors exhibited two simultaneous FGFR3 mutations.
- Two novel mutations (G380/382R and K650/652M) were previously linked to achondroplasia and SADDAN, respectively.
- The K650/652T mutation, found in bladder cancer, affects a codon implicated in other skeletal disorders.
Conclusions:
- The study identified novel FGFR3 mutations in bladder cancer, expanding the known mutational landscape.
- FGFR3 mutations found in non-lethal skeletal disorders may indicate an elevated risk for developing bladder tumors compared to the general population.
