description
Autosomal dominant mutations in FGFR2 are associated with the development of a range of skeletal disorders including Beare-Stevensen cutis gyrata syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome, Crouzon syndrome and Apert Syndrome (reveiwed in Burke, 1998; Webster and Donoghue 1997; Cunningham, 2007). Activating point mutations have also been identified in FGFR2 in ~15% of endometrial cancers, as well as to a lesser extent in ovarian and gastric cancers (Dutt, 2008; Pollock, 2007; Byron, 2010; Jang, 2001). Activating mutations in FGFR2 are thought to contribute to receptor activation through diverse mechanisms, including constitutive ligand-independent dimerization (Robertson, 1998), expanded range and affinity for ligand (Ibrahimi, 2004b; Yu, 2000) and enhanced kinase activity (Byron, 2008; Chen, 2007). FGFR2 amplifications have been identified in 10% of gastric cancers, where they are associated with poor prognosis diffuse cancers (Hattori, 1996; Ueda, 1999; Shin, 2000; Kunii, 2008) , and in ~1% of breast cancers (Turner, 2010; Tannheimer, 2000). FGFR2 amplification often occur in conjunction with deletions of C-terminal exons, resulting in expression of a internalization- and degradation-resistant form of the receptor (Takeda, 2007; Cha, 2008, 2009). Signaling through overexpressed FGFR2 shows evidence of being ligand-independent and sensitive to FGFR inhibitors (Lorenzi, 1997; Takeda, 2007; Cha, 2009). More recently, FGFR2 fusion proteins have been identified in a number of cancers; these are thought to form constitutive ligand-independent dimers based on the dimerization domains of the 3' fusion partners and contribute to cellular proliferation and tumorigenesis in a kinase-inhibitor sensitive manner (Wu, 2013; Arai, 2013; Seo, 2012; reviewed in Parker, 2014)

external resources
NCBI:1268870
REACTOME:R-HSA-1839126
PUBMED:15282208
PUBMED:17552943
PUBMED:9266968
PUBMED:17803937
PUBMED:9816310
PUBMED:18757403
PUBMED:11003564
PUBMED:20101236
PUBMED:18337450
PUBMED:9538690
PUBMED:17525745
PUBMED:10626794
PUBMED:11056689
PUBMED:18381441
PUBMED:11325814
PUBMED:9539778
PUBMED:19103595
PUBMED:9154000
PUBMED:20106510
PUBMED:17505008
PUBMED:18552176

genes
FGF1 , FGF2 , FGF3 , FGF4 , FGF5 , FGF6 , FGF7 , FGF8 , FGF9 , FGF10 , FGFR2 , GTF2F1 , GTF2F2 , NCBP1 , POLR2A , POLR2B , POLR2C , POLR2D , POLR2E , POLR2F , POLR2G , POLR2H , POLR2I , POLR2J , POLR2K , POLR2L , FGF23 , FGF18 , FGF17 , FGF16 , NCBP2 , FGF20 , FGF22 ,