FGFR3 (4;14) translocation mutants Dimerization of FGFR3 t(4;14) translocation mutants Authored: Rothfels, K, 2012-02-09 Edited: Rothfels, K, 2012-05-16 Pubmed10568829 Pubmed11157491 Pubmed11290605 Pubmed11429702 Pubmed19381019 Pubmed9207791 Pubmed9865713 Reactome Database ID Release 432038386 Reactome, http://www.reactome.org ReactomeREACT_120754 Reviewed: Ezzat, S, 2012-05-15 has a Stoichiometric coefficient of 2 ~15% of multiple myelomas contain translocations that put the FGFR3 gene under the control of the strong IGH locus (Chesi, 1997; Avet-Loiseau, 1998). This translocation results in the overexpresssion of FGFR3 (Chesi, 1997), which leads to aberrant signaling in either a ligand-dependent (Otsuki, 1999; Qing, 2009) or independent fashion (Chesi, 2001). Overexpression of WT FGFR3 results in a low level of FGF-independent MAPK activation, suggesting that overexpression can lead to ligand-independent dimerization; however this response is more pronounced after ligand-stimulation (Chesi, 2001; Qing, 2009). ~5% of multiple myelomas with FGFR3 translocations also contain coding sequence activating mutations (Chesi, 1997; Avet-Loiseau, 1998). These mutations (R248C, Y373C, K650E and K650M) mimic activating mutations seen in bone development disoders, are believed to arise later in tumor progression than the translocation event and contribute to ligand-independent signaling (Chesi, 1997; Chesi, 2001; Li, 2001; Ronchetti, 2001). FGFR3 (4;14) translocation mutant dimers