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Drug-sensitive FGFR2 mutations in endometrial carcinoma
- Dutt, Amit (author)
- Salvesen, Helga B (author)
- Chen, Tzu-Hsiu (author)
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- Ramos, Alex H (author)
- Onofrio, Robert C (author)
- Hatton, Charlie (author)
- Nicoletti, Richard (author)
- Winckler, Wendy (author)
- Grewal, Rupinder (author)
- Hanna, Megan (author)
- Wyhs, Nicolas (author)
- Ziaugra, Liuda (author)
- Richter, Daniel J (author)
- Trovik, Jone (author)
- Engelsen, Ingeborg B (author)
- Stefansson, Ingunn M (author)
- Fennell, Tim (author)
- Cibulskis, Kristian (author)
- Akslen, Lars A (author)
- Gabriel, Stacey (author)
- Wong, Kwok-Kin (author)
- Sellers, William R (author)
- Meyerson, Matthew (author)
- Greulich, Heidi (author)
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- (creator_code:org_t)
- 2008-06-24
- 2008
- English.
- In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 105:25, s. 8713-8717
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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.
Keyword
- endometrial cancer
- fibroblast growth factor receptor 2
- oncogene
- targeted therapy
- tyrosine kinase
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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- Nicoletti, Richa ...
- Winckler, Wendy
- Grewal, Rupinder
- Hanna, Megan
- Wyhs, Nicolas
- Ziaugra, Liuda
- Richter, Daniel ...
- Trovik, Jone
- Engelsen, Ingebo ...
- Stefansson, Ingu ...
- Fennell, Tim
- Cibulskis, Krist ...
- Zody, Michael C.
- Akslen, Lars A
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- Wong, Kwok-Kin
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- Greulich, Heidi
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