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Fibroblast growth factor receptor 3 (FGFR3) - analyses of the S249C mutation and protein expression in primary
H Dai1, R Holm, G B Kristensen
1Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, N-0310 0slo, Norway.
Abstract:
Fibroblast growth factor receptor 3 (FGFR3) seems to play an inhibitory role in bone development, as activating mutations in the gene underlie disorders such as achondroplasia and thanatophoric dysplasia. Findings from multiple myeloma (MM) indicate that FGFR3 also can act as an oncogene, and mutation of codon 249 in the fibroblast growth factor receptor 3 (FGFR3) gene was recently detected in 3/12 primary cervical carcinomas. We have analysed 91 cervical carcinomas for this specific S249C mutation using amplification created restriction site methodology (ACRS), and detected no mutations. Immunohistochemistry was performed on 73 of the tumours. Reduced protein staining was seen in 43 (58.8%) samples. Six of the tumours (8.2%) revealed increased protein staining compared with normal cervical tissue. These patients had a better prognosis than those with reduced or normal levels, although not statistically significant. This report weakens the hypothesis of FGFR3 as an oncogene of importance in cervical carcinomas.
Insights
Fibroblast growth factor receptor 3 (FGFR3) mutations were not found in cervical carcinomas. FGFR3 protein levels varied, but did not significantly correlate with patient prognosis, weakening its role as an oncogene in this cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Fibroblast growth factor receptor 3 (FGFR3) mutations are implicated in bone development disorders and multiple myeloma.
- Recent findings suggested a potential oncogenic role for FGFR3 in cervical carcinomas due to a specific mutation (S249C).
Purpose of the Study:
- To investigate the presence of the FGFR3 S249C mutation in a cohort of cervical carcinomas.
- To assess FGFR3 protein expression levels and their correlation with patient prognosis in cervical cancer.
Main Methods:
- Analysis of 91 cervical carcinomas for the FGFR3 S249C mutation using amplification created restriction site methodology (ACRS).
- Immunohistochemistry performed on 73 tumors to evaluate FGFR3 protein expression levels.
- Correlation analysis between mutation status, protein levels, and patient prognosis.
Main Results:
- No FGFR3 S249C mutations were detected in any of the 91 analyzed cervical carcinomas.
- Reduced FGFR3 protein staining was observed in 58.8% of tumors, while 8.2% showed increased staining compared to normal tissue.
- Patients with increased FGFR3 protein staining exhibited a trend towards better prognosis, though not statistically significant.
Conclusions:
- The specific FGFR3 S249C mutation is not a significant factor in cervical carcinogenesis.
- FGFR3 protein expression is altered in cervical tumors, but its prognostic significance requires further investigation.
- The hypothesis of FGFR3 as a key oncogene in cervical carcinomas is weakened by these findings.
