Signaling by FGFR4 in disease

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R-HSA-5655291
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Homo sapiens
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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).

Literature References
PubMed ID Title Journal Year
8845844 Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1)

Rousseau, F, El Ghouzzi, V, Delezoide, AL, Legeai-Mallet, L, Le Merrer, M, Munnich, A, Bonaventure, J

Hum Mol Genet 1996
9207791 Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3

Chesi, M, Nardini, E, Brents, LA, Schröck, E, Ried, T, Kuehl, WM, Bergsagel, PL

Nat Genet 1997
15448004 The fibroblast growth factor receptor-4 Arg388 allele is associated with prostate cancer initiation and progression

Wang, J, Stockton, DW, Ittmann, M

Clin Cancer Res 2004
11830541 Cancer progression and tumor cell motility are associated with the FGFR4 Arg(388) allele

Bange, J, Prechtl, D, Cheburkin, Y, Specht, K, Harbeck, N, Schmitt, M, Knyazeva, T, Müller, S, Gärtner, S, Sures, I, Wang, H, Imyanitov, E, Häring, HU, Knayzev, P, Iacobelli, S, Höfler, H, Ullrich, A

Cancer Res 2002
17525745 Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes

Pollock, PM, Gartside, MG, Dejeza, LC, Powell, MA, Mallon, MA, Davies, H, Mohammadi, M, Futreal, PA, Stratton, MR, Trent, JM, Goodfellow, PJ

Oncogene 2007
19946327 The FGFR4 Y367C mutant is a dominant oncogene in MDA-MB453 breast cancer cells

Roidl, A, Foo, P, Wong, W, Mann, C, Bechtold, S, Berger, HJ, Streit, S, Ruhe, JE, Hart, S, Ullrich, A, Ho, HK

Oncogene 2010
16012724 FGFR4 Gly388Arg polymorphism and prognosis of breast and colorectal cancer

Spinola, M, Leoni, VP, Tanuma, J, Pettinicchio, A, Frattini, M, Signoroni, S, Agresti, R, Giovanazzi, R, Pilotti, S, Bertario, L, Ravagnani, F, Dragani, TA

Oncol Rep 2005
18056464 Genetic alterations in the tyrosine kinase transcriptome of human cancer cell lines

Ruhe, JE, Streit, S, Hart, S, Wong, CH, Specht, K, Knyazev, P, Knyazeva, T, Tay, LS, Loo, HL, Foo, P, Wong, W, Pok, S, Lim, SJ, Ong, H, Luo, M, Ho, HK, Peng, K, Lee, TC, Bezler, M, Mann, C, Gaertner, S, Hoefler, H, Iacobelli, S, Peter, S, Tay, A, Brenner, S, Venkatesh, B, Ullrich, A

Cancer Res 2007
19809159 Identification of FGFR4-activating mutations in human rhabdomyosarcomas that promote metastasis in xenotransplanted models

Taylor JG, 6th, Cheuk, AT, Tsang, PS, Chung, JY, Song, YK, Desai, K, Yu, Y, Chen, QR, Shah, K, Youngblood, V, Fang, J, Kim, S, Yeung, C, Helman, LJ, Mendoza, A, Ngo, V, Staudt, LM, Wei, JS, Khanna, C, Catchpoole, D, Qualman, SJ, Hewitt, SM, Merlino, G, Chanock, SJ, Khan, J

J Clin Invest 2009
11157491 Activated fibroblast growth factor receptor 3 is an oncogene that contributes to tumor progression in multiple myeloma

Chesi, M, Brents, LA, Ely, SA, Bais, C, Robbiani, DF, Mesri, EA, Kuehl, WM, Bergsagel, PL

Blood 2001
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cancer 162 malignant tumor, malignant neoplasm, primary cancer
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