t(4;14) translocations of FGFR3

Stable Identifier
R-HSA-2033515
Type
Pathway
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

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).

Literature References
PubMed ID Title Journal Year
12835230 Mutation, SNP, and isoform analysis of fibroblast growth factor receptor 3 (FGFR3) in 150 newly diagnosed multiple myeloma patients

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

Blood 2003
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
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, Yamada, O, Yata, K, Sakaguchi, H, Kurebayashi, J, Nakazawa, N, Taniwaki, M, Yawata, Y, Ueki, A

Int J Oncol 1999
19381019 Antibody-based targeting of FGFR3 in bladder carcinoma and t(4;14)-positive multiple myeloma in mice

Qing, J, Du, X, Chen, Y, Chan, P, Li, H, Wu, P, Marsters, S, Stawicki, S, Tien, J, Totpal, K, Ross, S, Stinson, S, Dornan, D, French, D, Wang, QR, Stephan, JP, Wu, Y, Wiesmann, C, Ashkenazi, A

J Clin Invest 2009
16467200 The inhibitory anti-FGFR3 antibody, PRO-001, is cytotoxic to t(4;14) multiple myeloma cells

Trudel, S, Stewart, AK, Rom, E, Wei, E, Li, ZH, Kotzer, S, Chumakov, I, Singer, Y, Chang, H, Liang, SB, Yayon, A

Blood 2006
11429702 Deregulated FGFR3 mutants in multiple myeloma cell lines with t(4;14): comparative analysis of Y373C, K650E and the novel G384D mutations

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

Oncogene 2001
9865713 High incidence of translocations t(11;14)(q13;q32) and t(4;14)(p16;q32) in patients with plasma cell malignancies

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

Cancer Res 1998
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
17942756 The multiple myeloma associated MMSET gene contributes to cellular adhesion, clonogenic growth, and tumorigenicity

Lauring, J, Abukhdeir, AM, Konishi, H, Garay, JP, Gustin, JP, Wang, Q, Arceci, RJ, Matsui, W, Park, BH

Blood 2008
Participants
Participant Of
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed