Drug-sensitive FGFR2 mutations in endometrial carcinoma.

Proc Natl Acad Sci U S A
Authors
Keywords
Abstract

Oncogenic activation of tyrosine kinases is a common mechanism of carcinogenesis and, given the druggable nature of these enzymes, an attractive target for anticancer therapy. Here, we show that somatic mutations of the fibroblast growth factor receptor 2 (FGFR2) tyrosine kinase gene, FGFR2, are present in 12% of endometrial carcinomas, with additional instances found in lung squamous cell carcinoma and cervical carcinoma. These FGFR2 mutations, many of which are identical to mutations associated with congenital craniofacial developmental disorders, are constitutively activated and oncogenic when ectopically expressed in NIH 3T3 cells. Inhibition of FGFR2 kinase activity in endometrial carcinoma cell lines bearing such FGFR2 mutations inhibits transformation and survival, implicating FGFR2 as a novel therapeutic target in endometrial carcinoma.

Year of Publication
2008
Journal
Proc Natl Acad Sci U S A
Volume
105
Issue
25
Pages
8713-7
Date Published
2008 Jun 24
ISSN
1091-6490
URL
DOI
10.1073/pnas.0803379105
PubMed ID
18552176
PubMed Central ID
PMC2438391
Links
Grant list
U24 CA126546 / CA / NCI NIH HHS / United States