Drug-sensitive FGFR2 mutations in endometrial carcinoma

被引：298

作者：

Dutt, Amit ^{[1
,5
]}

Salvesen, Helga B. ^{[6
,9
]}

Chent, Tzu-Hsiu ^{[1
,5
]}

Ramos, Alex H. ^{[1
,5
]}

Onofrio, Robert C. ^{[5
]}

Hatton, Charlie ^{[2
,5
]}

Nicoletti, Richard ^{[1
,2
,5
]}

Winckler, Wendy ^{[2
,5
]}

Grewal, Rupinder ^{[2
,5
]}

Hanna, Megan ^{[2
,5
]}

Wyhs, Nicolas ^{[2
,5
]}

Ziaugra, Liuda ^{[2
,5
]}

Richter, Daniel J. ^{[2
,5
]}

Trovik, Jone ^{[5
,6
]}

Engelsen, Ingeborg B. ^{[6
,9
]}

Stefansson, Ingunn M. ^{[7
,8
]}

Fennell, Tim ^{[2
,5
]}

Cibulskis, Kristian ^{[2
,5
]}

Zody, Michael C. ^{[2
,5
]}

Akslen, Lars A. ^{[7
,8
]}

Gabriel, Stacey ^{[2
,5
]}

Wong, Kwok-Kin ^{[1
,3
]}

Sellers, William R. ^{[1
,10
]}

Meyerson, Matthew ^{[1
,2
,4
,5
]}

Greulich, Heidi ^{[1
,2
,3
,5
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[2] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

[5] MIT & Harvard, Broad Inst, Cambridge, MA 02142 USA

[6] Univ Bergen, Dept Clin Med, N-5020 Bergen, Norway

[7] Univ Bergen, Gade Inst, Sect Pathol, N-5020 Bergen, Norway

[8] Haukeland Hosp, Dept Pathol, N-5020 Bergen, Norway

[9] Haukeland Hosp, Dept Obstet & Gynecol, N-5020 Bergen, Norway

[10] Novartis Inst Biomed Res, Cambridge, MA 02139 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 25期

关键词：

endometrial cancer; fibroblast growth factor receptor 2; oncogene; targeted therapy; tyrosine kinase;

D O I：

10.1073/pnas.0803379105

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Oncogenic activation of tyrosine kinases is a common mechainism 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.

引用

页码：8713 / 8717

页数：5