PathwayStep4199 PathwayStep4194 Signaling by FGFR2 amplification mutants Activated point mutants of FGFR2 Signaling by FGFR2 mutants Authored: Rothfels, K, 2012-02-09 Edited: Rothfels, K, 2012-05-16 Pubmed17505008 Pubmed17552943 Pubmed18381441 Pubmed19147536 Pubmed21367659 Pubmed21711248 Pubmed9154000 Pubmed9538690 Reactome Database ID Release 431839126 Reactome, http://www.reactome.org ReactomeREACT_121155 Reviewed: Ezzat, S, 2012-05-15 The FGFR2 gene has been shown to be subject to activating mutations and gene amplification leading to a variety of proliferative and developmental disorders depending on whether these events occur in the germline or arise somatically. Activating FGFR2 mutations in the germline give rise to a range of craniosynostotic conditions including Pfeiffer, Apert, Jackson-Weiss, Crouzon and Beare-Stevensen Cutis Gyrata syndromes. These autosomal dominant skeletal disorders are characterized by premature fusion of several sutures in the skull, and in some cases also involve syndactyly (abnormal bone fusions in the hands and feet) (reviewed in Webster and Donoghue, 1997; Burke, 1998; Cunningham, 2007). <br><br>Activating FGFR2 mutations arising somatically have been linked to the development of gastric and endometrial cancers (reviewed in Greulich and Pollock, 2011; Wesche, 2011). Many of these mutations are similar or identical to those that contribute to the autosomal disorders described above. Notably, loss-of-function mutations in FGFR2 have also been recently described in melanoma (Gartside, 2009). FGFR2 may also contribute to tumorigenesis through overexpression, as FGFR2 has been identified as a target of gene amplification in gastric and breast cancers (Kunii, 2008; Takeda, 2007).