FGFR3 mutant receptor activation

Stable Identifier
Homo sapiens
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The FGFR3 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. As is the case for the other receptors, many of the activating mutations that are seen in FGFR3-related cancers mimic the germline FGFR3 mutations that give rise to autosomal skeletal disorders and include both ligand-dependent and independent mechanisms (reviewed in Webster and Donoghue, 1997; Burke et al, 1998; Wesche et al, 2011). In addition to activating mutations, the FGFR3 gene is subject to a translocation event in 15% of multiple myelomas (Avet-Loiseau et al, 1998; Chesi et al, 1997). This chromosomal rearrangement puts the FGFR3 gene under the control of the highly active IGH promoter and promotes overexpression and constitutive activation of FGFR3 (Otsuki et al, 1999). In a small proportion of multiple myelomas, the translocation event is accompanied by activating mutations in the FGFR3 coding sequence (Chesi et al, 1997; Onwuazor et al, 2003; Ronchetti et al, 2001).

Literature References
PubMed ID Title Journal Year
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

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

Nat Genet 1997
9538690 Fibroblast growth factor receptors: lessons from the genes

Burke, D, Malcolm, S, Blundell, TL, Wilkes, D

Trends Biochem Sci 1998
9865713 High incidence of translocations t(11;14)(q13;q32) and t(4;14)(p16;q32) in patients with plasma cell malignancies

Harousseau, JL, Talmant, P, Li, JY, Avet-Loiseau, H, Jaccard, A, Facon, T, Bataille, R, Rapp, MJ, Morineau, N, Trimoreau, F, Maloisel, F, Brigaudeau, C

Cancer Res 1998
21711248 Fibroblast growth factors and their receptors in cancer

Haglund, K, Wesche, J, Haugsten, EM

Biochem J 2011
11429702 Deregulated FGFR3 mutants in multiple myeloma cell lines with t(4;14): comparative analysis of Y373C, K650E and the novel G384D mutations

Otsuki, T, Lombardi, L, Colombo, G, Greco, A, Compasso, S, Neri, A, Ronchetti, D, Dell'Era, P

Oncogene 2001
9154000 FGFR activation in skeletal disorders: too much of a good thing

Donoghue, DJ, Webster, MK

Trends Genet 1997
12835230 Mutation, SNP, and isoform analysis of fibroblast growth factor receptor 3 (FGFR3) in 150 newly diagnosed multiple myeloma patients

Wen, XY, Onwuazor, ON, Masih-Khan, E, Barlogie, B, Zhuang, L, Stewart, AK, Claudio, J, Shaughnessy JD, Jr, Wang, DY

Blood 2003
10568829 Expression of fibroblast growth factor and FGF-receptor family genes in human myeloma cells, including lines possessing t(4;14)(q16.3;q32. 3) and FGFR3 translocation

Otsuki, T, Kurebayashi, J, Ueki, A, Sakaguchi, H, Taniwaki, M, Yamada, O, Yata, K, Nakazawa, N, Yawata, Y

Int J Oncol 1999
Name Identifier Synonyms
bone development disease DOID:0080006
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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