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PMID: 18552176 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Drug-sensitive FGFR2 mutations in endometrial carcinoma.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 105 ·No. 25 ·2008-06-24 ·Pages 8713-7

Dutt A, Salvesen HB, Chen TH, Ramos AH, Onofrio RC, Hatton C, Nicoletti R, Winckler W, Grewal R, Hanna M, Wyhs N, Ziaugra L, Richter DJ, Trovik J, Engelsen IB, Stefansson IM, Fennell T, Cibulskis K, Zody MC, Akslen LA, Gabriel S, Wong KK, Sellers WR, Meyerson M, Greulich H

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.

MeSH Terms
Animals Carcinoma/drug therapy,genetics,metabolism Cell Line, Tumor Cell Proliferation Cell Survival Endometrial Neoplasms/drug therapy,genetics,metabolism Female Mice Mutation NIH 3T3 Cells Receptor, Fibroblast Growth Factor, Type 2/antagonists & inhibitors,genetics,metabolism Transfection
Chemicals
Receptor, Fibroblast Growth Factor, Type 2
Authors & Affiliations
25 authors, click to expand affiliations / ORCID
Dutt Amit
Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Salvesen Helga B
Chen Tzu-Hsiu
Ramos Alex H
Onofrio Robert C
Hatton Charlie
Nicoletti Richard
Winckler Wendy
Grewal Rupinder
Hanna Megan
Wyhs Nicolas
Ziaugra Liuda
Richter Daniel J
Trovik Jone
Engelsen Ingeborg B
Stefansson Ingunn M
Fennell Tim
Cibulskis Kristian
Zody Michael C
Akslen Lars A
Gabriel Stacey
Wong Kwok-Kin
Sellers William R
Meyerson Matthew
Greulich Heidi
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0803379105
Published
2008-06-24
Epub
2008-00-13
Pages
8713-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2438391
Subset
IM
Grants
NCI NIH HHS · U24 CA126546 · United States
External Links
PubMed source DOI: 10.1073/pnas.0803379105 PMC Full Text View journal details
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