Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes

Oncogene. 2007 Nov 1;26(50):7158-62. doi: 10.1038/sj.onc.1210529. Epub 2007 May 21.


Endometrial carcinoma is the most common gynecological malignancy in the United States. Although most women present with early disease confined to the uterus, the majority of persistent or recurrent tumors are refractory to current chemotherapies. We have identified a total of 11 different FGFR2 mutations in 3/10 (30%) of endometrial cell lines and 19/187 (10%) of primary uterine tumors. Mutations were seen primarily in tumors of the endometrioid histologic subtype (18/115 cases investigated, 16%). The majority of the somatic mutations identified were identical to germline activating mutations in FGFR2 and FGFR3 that cause Apert Syndrome, Beare-Stevenson Syndrome, hypochondroplasia, achondroplasia and SADDAN syndrome. The two most common somatic mutations identified were S252W (in eight tumors) and N550K (in five samples). Four novel mutations were identified, three of which are also likely to result in receptor gain-of-function. Extensive functional analyses have already been performed on many of these mutations, demonstrating they result in receptor activation through a variety of mechanisms. The discovery of activating FGFR2 mutations in endometrial carcinoma raises the possibility of employing anti-FGFR molecularly targeted therapies in patients with advanced or recurrent endometrial carcinoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amino Acid Substitution / genetics
  • Bone Diseases, Developmental / genetics*
  • Carcinoma, Endometrioid / genetics*
  • Carcinosarcoma / genetics*
  • Cell Line, Tumor
  • Craniosynostoses / genetics*
  • Endometrial Neoplasms / genetics*
  • Female
  • Germ-Line Mutation*
  • Humans
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics*


  • FGFR2 protein, human
  • Receptor, Fibroblast Growth Factor, Type 2