title: Somatic mutations of fibroblast growth factor receptor 3 (FGFR3) are uncommon in carcinomas of the uterine cervix.
abstract: Germline mutations of the gene encoding human fibroblast growth factor receptor 3 (FGFR3) have been shown to be responsible for several related autosomal dominant forms of syndromic craniosynostosis and short limb dwarfism. Somatic activating mutations of FGFR3 were recently reported to occur in three of 12 (25%) uterine cervical carcinomas and nine of 26 (35%) bladder carcinomas, suggesting that constitutive activation of FGFR3 may be an important mechanism underlying the development and/or progression of these common epithelial malignancies. In order to investigate further a possible role for FGFR3 mutations in cervical carcinogenesis, we performed sequence-based mutational analysis of FGFR3 in 51 primary cervical carcinomas and seven cervical carcinoma-derived cell lines. The regions analysed (exons 7, 10, 13, 15, and 19) encompassed all previously described FGFR3 mutations. A single nucleotide substitution at codon 249, predicting a serine to cysteine amino acid substitution (S249C) in the FGFR3 extracellular domain, was identified in one primary tumor. Only wild type FGFR3 alleles were identified in the remaining tumors and cell lines. The S249C mutation is the only FGFR3 mutation described to date in cervical carcinomas. These findings suggest that while activating mutations of FGFR3 occur in cervical cancer, they may not be as common as initially reported.
authors: Department of Pathology, The University of Michigan Medical School, Ann Arbor 48109, USA.
authors: R
authors: R
authors: Wu
authors: D
authors: D
authors: Connolly
authors: C
authors: C
authors: Ngelangel
authors: F X
authors: FX
authors: Bosch
authors: N
authors: N
authors: Muñoz
authors: K R
authors: KR
authors: Cho
mesh_terms: D015152:Blotting, Northern; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense; D011505:Protein-Tyrosine Kinases; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3