|Tumor Type||Primary Site|
The receptor tyrosine kinase FGFR2 is one of four fibroblast growth factor receptors designated FGFR1-4 that activate FGF signalling upon trans-autophosphorylation of the receptor dimers. Some genetic alterations of FGFR2 lead to aberrant activation of FGFR2 signaling cascades due to the creation of autocrine signaling loop or the release of FGFR2 from autoinhibition. It is known that some FGFR2 gene variations including intronic polymorphisms confer a risk for breast cancer, preferentially for estrogen receptor-positive breast tumors. FGFR2 and FGF10, the main ligand of FGFR2, are both overexpressed in 5-10% of breast tumors. Somatic missense mutations have also been reported in breast cancer leading to ligand independent activation of FGFR2. In cell line and xenograft experiments, inhibition/knockdown of FGFR2 results in anti-tumour effects, suggesting the oncogenic role of FGFR2, raising the potential of FGFR2 as a target of therapy in FGFR2 driven cancers. The P253R variant in FGFR2 has also been described in some constitutional disorders including craniosynostosis syndromes (eg, Apert syndrome).