FGFR3 fusions dimerize

Stable Identifier
Reaction [transition]
Homo sapiens
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Constitutively active fusions of FGFR3 have been identified in glioblastoma, non-small cell lung cancer and bladder cancer, among others (Singh et al, 2012; Williams et al, 2013; Wu et al, 2013; Wang et al, 2014; Capelletti et al, 2014; Yuan et al, 2015; Carneiro et al, 2015; reviewed in Parker et al, 2014). The most prevalent fusion partner is TACC3 (transforming acidic coiled-coil-containing protein 3), a microtubule binding protein with roles in microtubule spindle assembly and chromosome segregation (Singh et al, 2014; Burgess et al, 2015; reviewed in Parker et al, 2014). There are conflicting reports about whether FGFR3 fusions form constitutive dimers, however ligand-independent autophosphorylation and downstream signaling has been demonstrated. FGFR3 fusions promote cellular proliferation and tumorigenesis and appear to escaped miRNA-mediated downregulation (Singh et al, 2012; Williams et al, 2013; Wu et al, 2013; Parker et al, 2013; reviewed in Parker et al, 2014).
Literature References
PubMed ID Title Journal Year
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
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
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
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
25246530 TACC3 protein regulates microtubule nucleation by affecting γ-tubulin ring complexes

Gireesh, KK, Singh, P, Manna, TK, Thomas, GE

J. Biol. Chem. 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
Functional status

Gain of function of FGFR3 fusions [plasma membrane]

Disease Entity
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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