Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans

Logie, Armelle, Dunois-Larde, Claire, Rosty, Christophe, Levrel, Olivier, Blanche, Martine, Ribeiro, Agnes, Gasc, Jean-Marie, Jorcano, Jose, Werner, Sabine, Sastre-Garau, Xavier, Thiery, Jean Paul and Radvanyi, Francois (2005) Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans. Human Molecular Genetics, 14 9: 1153-1160. doi:10.1093/hmg/ddi127


Author Logie, Armelle
Dunois-Larde, Claire
Rosty, Christophe
Levrel, Olivier
Blanche, Martine
Ribeiro, Agnes
Gasc, Jean-Marie
Jorcano, Jose
Werner, Sabine
Sastre-Garau, Xavier
Thiery, Jean Paul
Radvanyi, Francois
Title Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
1460-2083
Publication date 2005-05-01
Sub-type Article (original research)
DOI 10.1093/hmg/ddi127
Volume 14
Issue 9
Start page 1153
End page 1160
Total pages 8
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted abstract Specific germline activating point mutations in the gene encoding the tyrosine kinase receptor FGFR3 (fibroblast growth factor receptor 3) result in autosomal dominant human skeletal dysplasias. The identification in multiple myeloma and in two epithelial cancers—bladder and cervical carcinomas—of somatic FGFR3 mutations identical to the germinal activating mutations found in skeletal dysplasias, together with functional studies, have suggested an oncogenic role for this receptor. Although acanthosis nigricans, a benign skin tumor, has been found in some syndromes associated with germinal activating mutations of FGFR3, the role of activated FGFR3 in the epidermis has never been investigated. Here, we targeted an activated receptor mutant (S249C FGFR3) to the basal cells of the epidermis of transgenic mice. Mice expressing the transgene developed benign epidermal tumors with no sign of malignancy. These skin lesions had features in common with acanthosis nigricans and other benign human skin tumors, including seborrheic keratosis, one of the most common benign epidermal tumors in humans. We therefore screened a series of 62 cases of seborrheic keratosis for FGFR3 mutations. A large proportion of these tumors (39%) harbored somatic activating FGFR3 mutations, identical to those associated with skeletal dysplasia syndromes and bladder and cervical neoplasms. Our findings directly implicate FGFR3 activation as a major cause of benign epidermal tumors in humans.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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