Signaling by FGFR3 fusions in cancer

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Homo sapiens
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In recent years, recurrent fusions of FGFR3 have been identified in a number of cancers, including glioblastoma and cancers of the lung and bladder, among others (Singh et al, 2012; Parker et al, 2013; Williams et al, 2013; Wu et al, 2013; Capelletti et al, 2014; Yuan et al, 2014; Wang et al, 2014; Carneiro et al, 2015; reviewed in Parker et al, 2014). The most common fusion partner of FGFR3 is TACC3 (transforming acidic coiled coil protein 3), a protein involved in mitotic spindle assembly and chromosome segregation (Lin et al, 2010; Burgess et al, 2015). FGFR3 fusions are constitutively active and may form oligomers in a ligand-independent manner based on dimerization domains provided by the fusion partner (Singh et al, 2012; Williams et al, 2013; Parker et al, 2013; reviewed in Parker et al, 2014). Transformation and proliferation appear to be promoted through activation of the ERK and AKT signaling pathways. In contrast, PLC gamma signaling is not stimulated downstream of FGFR3 fusions, as the PLC gamma docking site is not present in the fusion. FGFR3 fusions are sensitive to protein kinase inhibitors, suggesting their potential as therapeutic targets (Singh et al, 2012; Williams et al, 2013; Wu et al, 2013; reviewed in Parker et al, 2014).
Literature References
PubMed ID Title Journal Year
26134678 Aurora-A-Dependent Control of TACC3 Influences the Rate of Mitotic Spindle Assembly

Cavazza, T, Joseph, N, Bayliss, R, Gergely, F, Vernos, I, Burgess, SG, Peset, I, Pfuhl, M

PLoS Genet. 2015
23298836 The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma

Parker, BC, Sun, Y, Granberg, KJ, Zhang, W, Liu, CG, Ji, P, Zheng, H, Li, X, Lang, FF, Haapasalo, H, Nykter, M, Cogdell, DE, Gumin, J, Chen, K, Liu, X, Hu, L, Sawaya, R, Annala, MJ, Fuller, GN, Yli-Harja, O, Visakorpi, T

J. Clin. Invest. 2013
23175443 Oncogenic FGFR3 gene fusions in bladder cancer

Knowles, MA, Williams, SV, Hurst, CD

Hum. Mol. Genet. 2013
23558953 Identification of targetable FGFR gene fusions in diverse cancers

Kalyana-Sundaram, S, Chinnaiyan, AM, Wang, R, Tomlins, SA, Ateeq, B, Cao, X, Cheng, AJ, Rhodes, DR, Hussain, MH, Kunju, LP, Lonigro, RJ, Robinson, DR, Sadis, S, Talpaz, M, Lin, SF, Pienta, KJ, Feng, FY, Roychowdhury, S, Vats, P, Wu, YM, Wyngaard, P, Su, F, Khazanov, N, Siddiqui, J, Zalupski, MM

Cancer Discov 2013
25535896 Recurrent FGFR3-TACC3 fusion gene in nasopharyngeal carcinoma

Zeng, MS, Yuan, L, Liu, ZH, Lin, ZR, Zhong, Q, Xu, LH

Cancer Biol. Ther. 2014
22837387 Transforming fusions of FGFR and TACC genes in human glioblastoma

Gao, Z, Sullivan, R, Niola, F, Guha, A, Zoppoli, P, Castano, A, Singh, D, Riccardi, R, Chan, JM, Finocchiaro, G, Aldape, K, Zagzag, D, Ceccarelli, M, Pellegatta, S, Porrati, P, Iavarone, A, Brat, DJ, Golfinos, JG, Rabadan, R, Qiu, K, Liu, EM, Mikkelsen, T, Reichel, J, Lasorella, A

Science 2012
24850843 FGFR1/3 tyrosine kinase fusions define a unique molecular subtype of non-small cell lung cancer

Luo, X, Sun, Y, Ye, T, Zhang, J, Shen, L, Pan, B, Pan, Y, Li, Y, Li, B, Chen, H, Zhang, Y, Wang, R, Ji, H, Wang, L, Li, H, Zhang, Y, Shen, X, Hu, H, Pao, W

Clin. Cancer Res. 2014
20566684 Clathrin heavy chain mediates TACC3 targeting to mitotic spindles to ensure spindle stability

Shih, HM, Lin, CH, Hu, CK

J. Cell Biol. 2010
25294908 Identification of recurrent FGFR3-TACC3 fusion oncogenes from lung adenocarcinoma

Lindeman, NI, Jänne, PA, Young, L, Munir, KJ, Stephens, PJ, Dodge, ME, Lipson, D, Jablons, DM, Richards, WG, Capelletti, M, Miller, VA, Kim, J, Park, SI, Hammerman, PS, Sasaki, H, Ercan, D

Clin. Cancer Res. 2014
24588013 Emergence of FGFR family gene fusions as therapeutic targets in a wide spectrum of solid tumours

Parker, BC, Zhang, W, Annala, M, Engels, M

J. Pathol. 2014
26425723 FGFR3-TACC3: A novel gene fusion in cervical cancer

Johnson, ML, Paintal, AS, Restrepo, A, Carneiro, BA, Ali, SM, Elvin, JA, Giles, FJ, Berry, E, Kamath, SD

Gynecol Oncol Rep 2015
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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