FGFR2 mutations are rare across histologic subtypes of ovarian cancer.
OBJECTIVE
Ovarian cancer is the leading cause of death from gynecologic malignancies in the Western world. Fibroblast growth factor receptor (FGFR) signaling has been implicated to play a role in ovarian tumorigenesis. Mutational activation of one member of this receptor family, FGFR2, is a frequent event in endometrioid endometrial cancer. Given the similarities in the histologic and molecular genetics of ovarian and endometrial cancers, we hypothesized that activating FGFR2 mutations may occur in a subset of endometrioid ovarian tumors, and possibly other histotypes.


METHODS
Six FGFR2 exons were sequenced in 120 primary ovarian tumors representing the major histologic subtypes.


RESULTS
FGFR2 mutation was detected at low frequency in endometrioid (1/46, 2.2%) and serous (1/41, 2.4%) ovarian cancer. No mutations were detected in clear cell, mucinous, or mixed histology tumors or in the ovarian cancer cell lines tested. Functional characterization of the FGFR2 mutations confirmed that the mutations detected in ovarian cancer result in receptor activation.


CONCLUSIONS
Despite the low incidence of FGFR2 mutations in ovarian cancer, the two FGFR2 mutations identified in ovarian tumors (S252W, Y376C) overlap with the oncogenic mutations previously identified in endometrial tumors, suggesting activated FGFR2 may contribute to ovarian cancer pathogenesis in a small subset of ovarian tumors.
Byron
Sara A
SA
Cancer and Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA.
Gartside
Michael G
MG
Wellens
Candice L
CL
Goodfellow
Paul J
PJ
Birrer
Michael J
MJ
Campbell
Ian G
IG
Pollock
Pamela M
PM
D002288:Adenocarcinoma, Mucinous / Q000235:genetics; D018269:Carcinoma, Endometrioid / Q000235:genetics; D018284:Cystadenocarcinoma, Serous / Q000235:genetics; D005091:Exons; D005260:Female; D006801:Humans; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*
C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2