Signaling by FGFR4 mutants

FGFR4 is perhaps the least well studied of the FGF receptors, and unlike the case for the other FGFR genes, mutations in FGFR4 are not known to be associated with any developmental disorders. Recently, however, somatically arising mutations in the FGFR4 coding sequence have begun to be identified in some cancers. 8% of rhabdomyosarcomas have activating mutations in the kinase domain of FGFR4. Two of these mutations - N535K (paralogous to the FGFR2 N550K allele found in endometrial cancers) and V550E - have been shown to support the oncogenic transformation of NIH 3T3 cells (Taylor, 2009). An FGFR4 Y367C mutation has also been identified in breast cancers (Ruhe, 2007; Roidl, 2010); mutations of paralogous residues in FGFR2 and FGFR3 are associated with both skeletal dysplasias and the development of diverse cancers (Pollock, 2007; Ruhe, 2007; Rousseau, 1996; Chesi, 1997, 2001).<br><br><br>Finally, a SNP at position 388 of FGFR4 is associated with aggressive disease development. Expression of the G388R allele in breast, colorectal and prostate cancers is correlated with rapid progression times and increased rates of recurrence and metastasis (Bange, 2002; Spinola, 2005; Wang, 2004). Edited: Rothfels, K, 2012-05-16 Authored: Rothfels, K, 2012-02-09 Reviewed: Ezzat, S, 2012-05-15

http://purl.obolibrary.org/obo/HINO_0016276

FGFR4 is perhaps the least well studied of the FGF receptors, and unlike the case for the other FGFR genes, mutations in FGFR4 are not known to be associated with any developmental disorders. Recently, however, somatically arising mutations in the FGFR4 coding sequence have begun to be identified in some cancers. 8% of rhabdomyosarcomas have activating mutations in the kinase domain of FGFR4. Two of these mutations - N535K (paralogous to the FGFR2 N550K allele found in endometrial cancers) and V550E - have been shown to support the oncogenic transformation of NIH 3T3 cells (Taylor, 2009). An FGFR4 Y367C mutation has also been identified in breast cancers (Ruhe, 2007; Roidl, 2010); mutations of paralogous residues in FGFR2 and FGFR3 are associated with both skeletal dysplasias and the development of diverse cancers (Pollock, 2007; Ruhe, 2007; Rousseau, 1996; Chesi, 1997, 2001).


Finally, a SNP at position 388 of FGFR4 is associated with aggressive disease development. Expression of the G388R allele in breast, colorectal and prostate cancers is correlated with rapid progression times and increased rates of recurrence and metastasis (Bange, 2002; Spinola, 2005; Wang, 2004).

Edited: Rothfels, K, 2012-05-16

Authored: Rothfels, K, 2012-02-09

Reviewed: Ezzat, S, 2012-05-15

Pubmed11157491

Pubmed15448004

Reactome, http://www.reactome.org

Pubmed8845844

Pubmed18056464

Pubmed19946327

Pubmed11830541

Pubmed19809159

Pubmed16012724

Pubmed17525745

Pubmed9207791

Signaling by FGFR4 mutants

http://purl.obolibrary.org/obo/NCBITaxon_9606

HINO:0016276

Signaling by FGFR4 mutants

ReactomeREACT_121286

Reactome Database ID Release 431839128

http://purl.obolibrary.org/obo/INO_0000021

http://purl.obolibrary.org/obo/HINO_0008160

http://purl.obolibrary.org/obo/HINO_0008108

http://purl.obolibrary.org/obo/HINO_0008109

http://purl.obolibrary.org/obo/HINO_0008107

http://purl.obolibrary.org/obo/HINO_0008174