PathwayStep4208 PathwayStep4209 Dimerization of FGFR3 t(4;14) translocation mutants Autocatalytic phosphorylation of FGFR3 t(4;14) translocation mutants t(4;14) translocations of FGFR3 Authored: Rothfels, K, 2012-02-09 Edited: Rothfels, K, 2012-05-16 Pubmed10568829 Pubmed11157491 Pubmed11429702 Pubmed12835230 Pubmed16467200 Pubmed17942756 Pubmed19381019 Pubmed9207791 Pubmed9865713 Reactome Database ID Release 432033515 Reactome, http://www.reactome.org ReactomeREACT_121011 Reviewed: Ezzat, S, 2012-05-15 Translocations which put the FGFR3 gene under the control of the strong IGH promoter have been identified in 15% of multiple myelomas (Avet-Loiseau, 1998; Chesi, 1997; Chesi, 2001). This translocation, which occurs 70kb upstream of the FGFR3 gene, also involves the nearby multiple myeloma SET-domain containing (MMSET) gene (Lauring, 2008), and although the contribution of each of these genes to the development of cancer has not been fully elucidated, several studies have shown that t(4:14) myeloma cell lines are sensitive to FGFR3 inhibitors (Trudel, 2006; Qing, 2009). In ~5% of cases, the translocation is accompanied by activating mutations of FGFR3 (Onwuazor, 2003; Ronchetti, 2001). The t(4;14) translocation results in overexpression of FGFR3 and subsequent ligand independent or anomalous ligand-dependent signaling (Otsuki, 1999).