Fibroblast Growth Factor Receptor (FGFR) Genes

Published Tue Jan 6, 2015


Fibroblast growth factor receptors (FGFRs) are transmembrane tyrosine kinase receptors whose genetic fusions are implicated in a broad range of cancers. FGFR genes encode a family of four homologous tyrosine kinase receptors: FGFR1, FGFR2, FGFR3, and FGFR4. These membrane-bound receptors initiate pathways important for normal organ, skeletal and vascular development by tightly regulating cell proliferation, survival, migration and differentiation(1,2). A consequence of diverse signaling targets, the FGFR genes are some of the most frequently amplified and mutated genes in cancer. Specifically, the constitutive and unregulated activation of FGFRs via genetic translocations, amplifications and point mutations can drive cancerous cell growth through various downstream mechanisms. Cancer-driving genetic mutations and translocations leading to constitutive activation of the FGFR tyrosine kinase domains present particularly promising targets for tyrosine kinase inhibitors (TKIs). The widespread oncogenic implication and potential targeted inhibition of FGFRs are driving further research towards detecting and characterizing these oncogenes.


FGFR signal transduction

Fibroblast growth factors (FGFs) and the FGFR signaling pathway play significant roles in cellular processes, including cell survival, adhesion, chemotaxis, apoptosis, migration and proliferation (3). The pathway is initiated by one of the 18 mammalian FGFs binding to one of the 4 homologous tyrosine kinase fibroblast growth receptors (FGFR1, FGFR2, FGFR3 or FGFR4) (4,5). The receptors are composed of an extracellular ligand-binding domain, a single hydrophobic transmembrane domain and a cytoplasmic domain containing the catalytic, split tyrosine kinase core (6,7). A variety of FGFR isoforms can result from alternative splicing of FGFR transcripts. The third immunoglobulin (Ig)-like domain, D3, is particularly sensitive to alternative exon usage which greatly alters ligand-binding between the three isoforms per receptor (8,9). The FGFs bind to FGFRs through simultaneous, low-affinity binding to the surface protein heparin sulphate glycosaminoglycan (HSGAG) (10). The now-functional FGFR-FGF-HSGAG ternary complexes then dimerize, bringing the kinase domains into close proximity to initiate transphosphorylation of tyrosine residues that act as docking sites for downstream effectors.


Figure 1 shows the FGFR-FGF-HSGAG complex. FGF interacts with FGFR through a heparin surface molecule, promoting dimerization of FGFR and transphosphorylation of the kinase domains. Most transcript isoforms of FGFR consist of a 5' untranslated region, three Ig-like domains, the third being especially susceptible to alternative splicing and the peptides of which influence cellular differentiation and FGF specificity. An acid box and heparin-binding motif constitute the region between the first and second Ig domains. A juxtamembrane domain separates the Ig-like domain from the tyrosine kinase domain.

Downstream signaling occurs via two main pathways, beginning with recruitment and phosphorylation of target proteins at the receptor's cytoplasmic tail. Shc, phospholipase-Cγ (PLCγ), Gab1, FRS2, and STAT1 are phosphorylated by FGFR stimulation (5). Activation of these proteins precludes many multifactorial and complex pathways critical in the control of cell migration, survival, shape, differentiation and proliferation. Recognizable pathways include the Ras-independent phosphoinositide 3-kinase (PI3K)-AKT and Ras-dependent mitogen-activated protein kinase (MAPK) signaling pathways, upregulated by the intracellular receptor substrates PLCγ and FRS (21,11,12). FGFR-initiated pathways are tightly regulated by feedback mechanisms and inhibitory proteins like SPRY and SEF13.


Figure 2 shows the major components of the FGFR-mediated signaling pathway. Upon activation of the tyrosine kinase domain activation recruits PLCγ and FRS2, which function as key adaptor proteins for downstream pathways. FRS2 initiates downstream signaling including MAPK and PI3K activation. MAPK3, Sprouty (SPRY) proteins and SEF family members negatively regulate FGFR activity (1,2,12).

FGFR translocations

Chromosomal translocations that result in subsequent FGFR fusion proteins are lineage-independent and have been directly linked to oncogenesis in a growing number of cancers, including hematological malignancies (14-27), cholangiocarcinomas (28-30), lung cancer (29,31,32), bladder cancer (33), prostate cancer (29), breast cancer (29,34), glioblastoma (35,36), alveolar rhabdosarcomas (37), pleomorphic salivary gland adenomas (37), gastric cancer (38), thyroid cancer (29) and head and neck squamous cell carcinoma (33).

Oncogenic tyrosine kinase translocations can occur at various regions; however, not all gene fusions produce biologically active proteins. Some FGFR translocations result in variants with an N-terminal domain of the fusion partner fused to the C-terminal end of FGFR that includes the kinase domain but not the transmembrane domain. No longer membrane bound or receptor-specific, the fusion proteins reside in the cytosol and are permanently dimerized and continuously signaling. These cytosolic fusion proteins escape normal down-regulation and feedback inhibition routes and are not degraded in lysosomes, resulting in long-term constitutive signaling (39). For example, the FGFR3-TACC3 fusion prevalent in 3% of glioblastoma mulitforme escapes microRNA-mediated regulation because the 3'-untranslated region is lost in the fusion transcript (35,40). The cytosolic tyrosine kinases cause aberrant signaling and unregulated activation of various intracellular pathways, including those discussed previously.

In some cases, chromosomal translocations occur upstream of the transmembrane domain, adopting the partner protein's ligand binding region and changing ligand specificity or ligand binding regulation. This sometimes results in the upregulation of downstream signaling or oligomerization of the tyrosine kinase domain (29). In other cases fusions can occur downstream of the tyrosine kinase domain, leading to aberrant signaling (29). Each unique fusion presents its own challenge for researchers, including detection, understanding the mechanism of action, and the creation of accompanying targeted therapeutics. The fusions associated with FGR1, FGFR2 and FGFR3 are discussed below.

FGFR1 translocations

The FGFR1 gene is located on chromosome 8, with 22 exons spanning 57,697 bases from 8p11.23 to p11.22. The canonical isoform of the expressed protein is 822 amino acids long. Translocations involving FGFR1 have been implicated in various types of cancer including hematological malignancies (14-25), glioblastomas (35), breast cancer (29,34), pleomorphic salivary gland adenocarcinomas (37), lung cancer (29), alveolar rhabdomyosarcoma (41) and bladder cancer (42).

A common FGFR1 translocation with an especially poor prognosis is 8p11 myeloproliferative syndrome (EMS), a common precursor of acute myeloid leukemia (AML) and is frequently accompanied by T- and B-cell lymphomas. EMS is characterized by a translocation at the 8p11 locus involving the FGFR1 gene and various fusion partners (43). Typically, the fusion transcripts encode proteins with the N-terminus of the translocation partner and the tyrosine kinase domain of FGFR1 in the C-terminus, resulting in constitutive FGFR1 signaling and promotion of the downstream pathways (34,44).

FGFR1 fusions and associated diseases
Fusion Disease Citation
CNTRL-FGFR1 EMS, AML, CML, T-cell lymphoma 15
TPR-FGFR1 EMS, MPN T-lymphoblastic lymphoma 45
ZMYM2-FGFR1 EMS, MPN, ALL, CMD, T-lymphoblastic lymphoma 25
FGFR1-PLAG1 Pleomorphic salivary gland adenocarcinomas 37
FOXO1-FGFR1 Alveolar rhabdomyosarcoma 41
ERLIN2-FGFR1 Breast cancer 29
FGFR1-ZNF703 Breast cancer 34
FGFR1-TACC1 Glioblastoma Multiforme 35
FGFR1-NTM Bladder cancer 42

FGFR2 translocations

The FGFR2 gene is a paralog to FGFR1 and is located on chromosome 10. The gene spans 120,129 bases from 10q25.3 to q26, and the expressed protein comprises 821 amino acids. Translocations involving FGFR2 were only recently identified. However, research within the last few years alone has revealed a large number of FGFR2 translocations, hinting that many more are to follow. So far, fusions have been found in cholangiocarcinoma (29,46), breast cancer (29), prostate cancer (29), lung cancer (29,31), intrahepatic cholangiocarcinoma (28,30), thyroid cancer (29) and gastric cancer (38).

FGFR2 fusions and associated diseases
Fusion Disease Citation
SLC45A3-FGFR2 Prostate cancer 29
CD44-FGFR2 Gastric cancer 38
FGFR2-TACC3 Intrahepatic cholangiocarcinoma 28
FGFR2-MGEA5 Intrahepatic cholangiocarcinoma 28
FGFR2-AHCYL1 Cholangiocarcinoma 46
FGFR2-KIAA1598 Intrahepatic cholangiocarcinoma 30
FGFR2-CCDC6 Cholangiocarcinoma, Breast cancer 29
FGFR2-BICC1 Cholangiocarcinoma 29
FGFR2-AFF3 Breast cancer 29
FGFR2-CASP7 Breast cancer 29
FGFR2-CCAR2 Lung squamous cell carcinoma 29
FGFR2-CIT Lung adenocarcinoma 31
FGFR2-OFD1 Thyroid cancer 29

FGFR3 translocations

The FGFR3 gene is located on chromosome 4p16.3. The gene consists of 15,566 bases and expresses a protein 806 amino acids long. Fusions of the FGFR3 gene have been implicated in peripheral T-cell lymphoma (27), bladder cancer (29,33,42), head and neck squamous cell cancer (29), non-small cell lung cancer (NSCLC) lung cancer (29,32) and glioblastoma (40). FGFR3 is implicated as an oncogene in 80% of low-grade non-invasive bladder tumors and is unregulated in about 40% of invasive bladder tumors (47). The FGFR3-TACC3 fusion is the most prevalent fusion in bladder cancer, but FGFR-BAI1AP2L1 in-frame fusions are also implicated in bladder cancer (33). Transforming acidic coiled-coil-containing protein 3 (TACC3) is also a fusion partner of FGFR3 in glioblastoma multiforme and lung squamous cell carcinomas (29,40). In the latter disease, the rearrangement includes the first 18 exons of FGFR3 upstream of the last 7 exons of TACC3. The resulting fusion protein has the last 226 amino acids of TACC3 directly appended to the FGFR3 protein.

FGFR3 fusions and associated diseases
Fusion Disease Citation
ETV6-FGFR3 Peripheral T-cell lymphoma 27
FGFR3-BAIAP2L1 Bladder cancer 33
FGFR3-TACC3 NSCLC, Glioblastoma Multiforme, Oral cancer, HNSCC, SCC 32,33,40
FGFR3-ELAVL3 Glioblastoma Multiforme 36
FGFR3-JAKMIP1 Bladder cancer 42

Tyrosine kinase inhibitors (TKIs)

FGFR genomic abnormalities are common in both hematological malignancies and solid tumors. The widespread amplifications, mutations and translocations of FGFR in various cancers drive research and development of small-molecule tyrosine kinase inhibitors (TKIs), which have the ability to target and inhibit constitutively active FGFR fusions. Most multi-kinase TKIs and selective FGFR inhibitors inhibit the ATP-binding domain, while some compete with FGFs for binding to the extracellular domain.

TKI Synonyms About
AZ12908010   Small molecule FGFR-selective inhibitor targeting kinase insert domain of FGFR 1-3 (48)
AZD4547   Small molecule FGFR-selective inhibitor that targets the kinase insert domain receptor of FGFR1-3. Inhibits kinase activity and growth in various cell lines with deregulated FGFR activity. (48)
Brivanib BMS-582664, brivanib alaninate Small molecule FGFR1 inhibitor that decreases receptor autophosphorylation, inhibits bFGF-induced tyrosine kinase activity and reduces phosphorylation of ERK and AKT in breast cancer with FGFR1 amplified cells (49)
Danusertib PHA-739358 Aurora kinase inhibitor that also inhibits FGFR1 and may exhibit antitumor activity (50)
Dasatinib BMS-354825, Sprycel, BMS 354825 Abl and Src family kinase inhibitor reduced growth in mouse models with pro-B lymphoma cells with FGFR1-ZMT2, FGFR1-BCR, FGFR1-CEP110 fusions (51)
Dovitinib CHIR-258, DOVITINIB LACTATE, TKI258, Multi-target TKI that inhibits proliferation in FGFR1 and FGFR2 amplified breast cancer cell lines showed inhibited proliferation and survival in EMS-related FGF1OP2-FGFR1, ZNF198-FGFR1 and BCR-FGFR1 positive cell lines (52,53)
ENMD-2076 ENMD-981693 Small molecule kinase inhibitor with sustained inhibition of FGFR1 and FGFR2. ENMD-2076 has inhibited the in vitro growth of a range of solid tumor and hematopoietic cancer cell lines (54)
Foretinib GSK1363089 Multi-kinase inhibitor that was found to have inhibitory effects on FGFR2 amplification through the blocking of inter-RTK signaling networks in KATO-III, gastric carcinoma cell lines (55)
Lenvatinib E-7080, LENVATINIB MESYLATE, Multi-targeted kinase inhibitor that has been shown to inhibit tumor angiogenesis by inhibiting FGFR signaling in endothelial cells (56)
Lucitabin E-3810, AL3810 Small molecule, potent inhibitor of multiple tyrosine kinases involved in angiogenisis, including FGFR1. It has been found that AL3810 inhibited autophosphorylation of FGFR1 in endothelial cells (57)
Midostaurin CGP 41251, N-Benzoyl-Staurosporine, N-Benzoylstaurosporine Small molecule TKI that has been found to inhibit ZNF198-FGFR1 tyrosine kinase activity (58)
Nintedanib BIBF 1120, Intedanib, Vargatef Small molecule triple tyrosine kinase inhibitor of FGFR1-3 that has increased overall survival in NSCLC (25119062). Seems to be effective in various other tumor types like prostate, colorectal, hepatocellular carcinoma, and gynecological tumors (59)
NVP-BGJ398 BGJ398 Selective FGFR inhibitor that inhibits proliferation in a number of cancer cell lines positive for FGFR genetic alterations, including FGFR1 and FGFR3 translocations (60 61)
Orantinib Orantinibum, SU 006668, Sugen TSU68 Small molecule inhibitor of FGFR1. Has induced inhibition of agiogenic receptor tyrosine kinase activity in vivo, leading to broad antitumor effects (62)
Pazopanib GW786034B, PAZOPANIB HYDROCHLORIDE, Votrient Potent and selective multi-targeted tyrosine kinase inhibitor FGFR2-TACC3 (28,63)
PD173074   ATP-competitive inhibition of FGFR kinase activity in vitro. Inhibits growth and induces apoptosis in ZFN198-FGFR1 expressed cells (64)
PKC412   Small molecule FGFR inhibitor found to have inhibitory effects on patient with myeloproliferative disorder positive for ZNF198-FGFR1 fusion (58)
Ponatinib AP24534 Multi-targeted TKI targeting CML patients with BCR-ABL. Found to have anti-tumor effects on 14 FGFR-deregulated cell lines. Reduces FGFR1-mediated signaling and inhibits cell growth65. Accompanied reduction and tumor necrosis in FGFR2-MGEA4 fusion (28)
Regorafenib BAY 73-4506, Stivarga Small molecule multi-kinase inhibitor that shows survival benefits in metastatic colorectal cancer (66)
Sunitinib SU-11248, Sutent Multi-targeted TKI that inhibits FGFR1 activity. Sunitinib differentially inhibited growth of cells expressing ZNF198-FGFR1 (64)
Vandetanib AZD-6474, Zactima Small molecule TKI shown to inhibit growth in cells with ZNF198-FGFR1 fusion (64)

Although the list of TKIs being studied continues to grow, research is still needed to identify novel fusion partners and understand their mechanisms of action. Fortunately, through the widespread adoption of next-generation sequencing (NGS), research on genetic abnormalities in cancer has significantly accelerated. NGS-based fusion detection has recently benefited from advancements like Anchored Multiplex PCR (AMP™) that allows for discovery of novel fusions in a scalable manner, while bioinformatics tools have helped to convert that information into usable data. Through the clever applications of these types of tools, the cancer research community is poised to make groundbreaking discoveries to further understand the biology and targeting of genes such as the FGFR gene family.

Want to learn how Archer FusionPlex NGS assays detect FGFR mutations?

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  1. Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010;10(2):116–129. doi:10.1038/nrc2780.
  2. Dienstmann R, Rodon J, Prat A, et al. Genomic aberrations in the FGFR pathway: opportunities for targeted therapies in solid tumors. Ann Oncol. 2014;25(3):552–563. doi:10.1093/annonc/mdt419.
  3. Böttcher RT, Niehrs C. Fibroblast growth factor signaling during early vertebrate development. Endocr Rev. 2005;26(1):63–77. doi:10.1210/er.2003-0040.
  4. Beenken A, Mohammadi M. The FGF family: biology, pathophysiology and therapy. Nat Rev Drug Discov. 2009;8(3):235–253. doi:10.1038/nrd2792.
  5. Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005;16(2):139–149. doi:10.1016/j.cytogfr.2005.01.001.
  6. Mohammadi M, Olsen SK, Ibrahimi OA. Structural basis for fibroblast growth factor receptor activation. Cytokine Growth Factor Rev. 2005;16(2):107–137. doi:10.1016/j.cytogfr.2005.01.008.
  7. Schlessinger J, Plotnikov AN, Ibrahimi OA, et al. Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization. Mol Cell. 2000;6(3):743–750.
  8. Johnson DE, Lu J, Chen H, Werner S, Williams LT. The human fibroblast growth factor receptor genes: a common structural arrangement underlies the mechanisms for generating receptor forms that differ in their third immunoglobulin domain. Mol Cell Biol. 1991;11(9):4627–4634.
  9. Miki T, Bottaro DP, Fleming TP, et al. Determination of ligand-binding specificity by alternative splicing: two distinct growth factor receptors encoded by a single gene. Proc Natl Acad Sci USA. 1992;89(1):246–250.
  10. Goetz R, Beenken A, Ibrahimi OA, et al. Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members. Mol Cell Biol. 2007;27(9):3417–3428. doi:10.1128/MCB.02249-06.
  11. Brooks AN, Kilgour E, Smith PD. Molecular pathways: fibroblast growth factor signaling: a new therapeutic opportunity in cancer. Clin Cancer Res. 2012;18(7):1855–1862. doi:10.1158/1078-0432.CCR-11-0699.
  12. Kouhara H, Hadari YR, Spivak-Kroizman T, et al. A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway. Cell. 1997;89(5):693–702.
  13. Thisse B, Thisse C. Functions and regulations of fibroblast growth factor signaling during embryonic development. Dev Biol. 2005;287(2):390–402. doi:10.1016/j.ydbio.2005.09.011.
  14. Demiroglu A, Steer EJ, Heath C, et al. The t(8;22) in chronic myeloid leukemia fuses BCR to FGFR1: transforming activity and specific inhibition of FGFR1 fusion proteins. Blood. 2001;98(13):3778–3783.
  15. Park TS, Song J, Kim JS, et al. 8p11 myeloproliferative syndrome preceded by t(8;9)(p11;q33), CEP110/FGFR1 fusion transcript: morphologic, molecular, and cytogenetic characterization of myeloid neoplasms associated with eosinophilia and FGFR1 abnormality. Cancer Genet Cytogenet. 2008;181(2):93–99. doi:10.1016/j.cancergencyto.2007.11.011.
  16. Hidalgo-Curtis C, Chase A, Drachenberg M, et al. The t(1;9)(p34;q34) and t(8;12)(p11;q15) fuse pre-mRNA processing proteins SFPQ (PSF) and CPSF6 to ABL and FGFR1. Genes Chromosomes Cancer. 2008;47(5):379–385. doi:10.1002/gcc.20541.
  17. Wasag B, Lierman E, Meeus P, Cools J, Vandenberghe P. The kinase inhibitor TKI258 is active against the novel CUX1-FGFR1 fusion detected in a patient with T-lymphoblastic leukemia/lymphoma and t(7;8)(q22;p11). Haematologica. 2011;96(6):922–926. doi:10.3324/haematol.2010.036558.
  18. Grand EK, Grand FH, Chase AJ, et al. Identification of a novel gene, FGFR1OP2, fused to FGFR1 in 8p11 myeloproliferative syndrome. Genes Chromosomes Cancer. 2004;40(1):78–83. doi:10.1002/gcc.20023.
  19. Mano Y, Takahashi K, Ishikawa N, et al. Fibroblast growth factor receptor 1 oncogene partner as a novel prognostic biomarker and therapeutic target for lung cancer. Cancer Sci. 2007;98(12):1902–1913. doi:10.1111/j.1349-7006.2007.00610.x.
  20. Guasch G, Popovici C, Mugneret F, et al. Endogenous retroviral sequence is fused to FGFR1 kinase in the 8p12 stem-cell myeloproliferative disorder with t(8;19)(p12;q13.3). Blood. 2003;101(1):286–288. doi:10.1182/blood-2002-02-0577.
  21. Gervais C, Dano L, Perrusson N, et al. A translocation t(2;8)(q12;p11) fuses FGFR1 to a novel partner gene, RANBP2/NUP358, in a myeloproliferative/myelodysplastic neoplasm. Leukemia. 2013;27(5):1186–1188. doi:10.1038/leu.2012.286.
  22. Soler G, Nusbaum S, Varet B, et al. LRRFIP1, a new FGFR1 partner gene associated with 8p11 myeloproliferative syndrome. Leukemia. 2009;23(7):1359–1361. doi:10.1038/leu.2009.79.
  23. Walz C, Chase A, Schoch C, et al. The t(8;17)(p11;q23) in the 8p11 myeloproliferative syndrome fuses MYO18A to FGFR1. Leukemia. 2005;19(6):1005–1009. doi:10.1038/sj.leu.2403712.
  24. Belloni E, Trubia M, Gasparini P, et al. 8p11 myeloproliferative syndrome with a novel t(7;8) translocation leading to fusion of the FGFR1 and TIF1 genes. Genes Chromosomes Cancer. 2005;42(3):320–325. doi:10.1002/gcc.20144.
  25. Buijs A, van Wijnen M, van den Blink D, van Gijn M, Klein SK. A ZMYM2-FGFR1 8p11 myeloproliferative neoplasm with a novel nonsense RUNX1 mutation and tumor lysis upon imatinib treatment. Cancer Genet. 2013;206(4):140–144. doi:10.1016/j.cancergen.2013.04.001.
  26. Vizmanos JL, Hernández R, Vidal MJ, et al. Clinical variability of patients with the t(6;8)(q27;p12) and FGFR1OP-FGFR1 fusion: two further cases. Hematol J. 2004;5(6):534–537. doi:10.1038/sj.thj.6200561.
  27. Yagasaki F, Wakao D, Yokoyama Y, et al. Fusion of ETV6 to fibroblast growth factor receptor 3 in peripheral T-cell lymphoma with a t(4;12)(p16;p13) chromosomal translocation. Cancer Res. 2001;61(23):8371–8374.
  28. Borad MJ, Champion MD, Egan JB, et al. Integrated genomic characterization reveals novel, therapeutically relevant drug targets in FGFR and EGFR pathways in sporadic intrahepatic cholangiocarcinoma. Horwitz MS, ed. PLoS Genet. 2014;10(2):e1004135. doi:10.1371/journal.pgen.1004135.
  29. Wu Y-M, Su F, Kalyana-Sundaram S, et al. Identification of targetable FGFR gene fusions in diverse cancers. Cancer Discov. 2013;3(6):636–647. doi:10.1158/2159-8290.CD-13-0050.
  30. Ross JS, Wang K, Gay L, et al. New routes to targeted therapy of intrahepatic cholangiocarcinomas revealed by next-generation sequencing. Oncologist. 2014;19(3):235–242. doi:10.1634/theoncologist.2013-0352.
  31. Seo J-S, Ju YS, Lee W-C, et al. The transcriptional landscape and mutational profile of lung adenocarcinoma. Genome Res. 2012;22(11):2109–2119. doi:10.1101/gr.145144.112.
  32. Majewski IJ, Mittempergher L, Davidson NM, et al. Identification of recurrent FGFR3 fusion genes in lung cancer through kinome-centred RNA sequencing. J Pathol. 2013;230(3):270–276. doi:10.1002/path.4209.
  33. Williams SV, Hurst CD, Knowles MA. Oncogenic FGFR3 gene fusions in bladder cancer. Hum Mol Genet. 2013;22(4):795–803. doi:10.1093/hmg/dds486.
  34. Xiao S, Nalabolu SR, Aster JC, et al. FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome. Nat Genet. 1998;18(1):84–87. doi:10.1038/ng0198-84.
  35. Singh D, Chan JM, Zoppoli P, et al. Transforming fusions of FGFR and TACC genes in human glioblastoma. Science. 2012;337(6099):1231–1235. doi:10.1126/science.1220834.
  36. Stransky N, Cerami E, Schalm S, Kim JL, Lengauer C. The landscape of kinase fusions in cancer. Nat Commun. 2014;5:4846. doi:10.1038/ncomms5846.
  37. Persson F, Winnes M, Andrén Y, et al. High-resolution array CGH analysis of salivary gland tumors reveals fusion and amplification of the FGFR1 and PLAG1 genes in ring chromosomes. Oncogene. 2008;27(21):3072–3080. doi:10.1038/sj.onc.1210961.
  38. Kim H-P, Cho G-A, Han S-W, et al. Novel fusion transcripts in human gastric cancer revealed by transcriptome analysis. Oncogene. 2013. doi:10.1038/onc.2013.490.
  39. Wesche J, Haglund K, Haugsten EM. Fibroblast growth factors and their receptors in cancer. Biochem J. 2011;437(2):199–213. doi:10.1042/BJ20101603.
  40. Parker BC, Annala MJ, Cogdell DE, et al. The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma. J Clin Invest. 2013;123(2):855–865. doi:10.1172/JCI67144.
  41. Liu J, Guzman MA, Pezanowski D, et al. FOXO1-FGFR1 fusion and amplification in a solid variant of alveolar rhabdomyosarcoma. Mod Pathol. 2011;24(10):1327–1335. doi:10.1038/modpathol.2011.98.
  42. Ross JS, Wang K, Al-Rohil RN, et al. Advanced urothelial carcinoma: next-generation sequencing reveals diverse genomic alterations and targets of therapy. Mod Pathol. 2014;27(2):271–280. doi:10.1038/modpathol.2013.135.
  43. Goradia A, Bayerl M, Cornfield D. The 8p11 myeloproliferative syndrome: review of literature and an illustrative case report. Int J Clin Exp Pathol. 2008;1(5):448–456.
  44. Jackson CC, Medeiros LJ, Miranda RN. 8p11 myeloproliferative syndrome: a review. Hum Pathol. 2010;41(4):461–476. doi:10.1016/j.humpath.2009.11.003.
  45. Kim SY, Kim J-E, Park S, Kim HK. Molecular identification of a TPR-FGFR1 fusion transcript in an adult with myeloproliferative neoplasm, T-lymphoblastic lymphoma, and a t(1;8)(q25;p11.2). Cancer Genet. 2014;207(6):258–262. doi:10.1016/j.cancergen.2014.05.011.
  46. Arai Y, Totoki Y, Hosoda F, et al. Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma. Hepatology. 2014;59(4):1427–1434. doi:10.1002/hep.26890.
  47. di Martino E, Tomlinson DC, Knowles MA. A Decade of FGF Receptor Research in Bladder Cancer: Past, Present, and Future Challenges. Adv Urol. 2012;2012(6):429213–10. doi:10.1155/2012/429213.
  48. Chell V, Balmanno K, Little AS, et al. Tumour cell responses to new fibroblast growth factor receptor tyrosine kinase inhibitors and identification of a gatekeeper mutation in FGFR3 as a mechanism of acquired resistance. Oncogene. 2013;32(25):3059–3070. doi:10.1038/onc.2012.319.
  49. Shiang CY, Qi Y, Wang B, et al. Amplification of fibroblast growth factor receptor-1 in breast cancer and the effects of brivanib alaninate. Breast Cancer Res Treat. 2010;123(3):747–755. doi:10.1007/s10549-009-0677-6.
  50. Meulenbeld HJ, Mathijssen RH, Verweij J, de Wit R, de Jonge MJ. Danusertib, an aurora kinase inhibitor. Expert Opin Investig Drugs. 2012;21(3):383–393. doi:10.1517/13543784.2012.652303.
  51. Ren M, Qin H, Ren R, Tidwell J, Cowell JK. Src activation plays an important key role in lymphomagenesis induced by FGFR1 fusion kinases. Cancer Res. 2011;71(23):7312–7322. doi:10.1158/0008-5472.CAN-11-1109.
  52. Chase A, Grand FH, Cross NCP. Activity of TKI258 against primary cells and cell lines with FGFR1 fusion genes associated with the 8p11 myeloproliferative syndrome. Blood. 2007;110(10):3729–3734. doi:10.1182/blood-2007-02-074286.
  53. Andre F, Bachelot T, Campone M, et al. Targeting FGFR with dovitinib (TKI258): preclinical and clinical data in breast cancer. Clin Cancer Res. 2013;19(13):3693–3702. doi:10.1158/1078-0432.CCR-13-0190.
  54. Fletcher GC, Brokx RD, Denny TA, et al. ENMD-2076 is an orally active kinase inhibitor with antiangiogenic and antiproliferative mechanisms of action. Mol Cancer Ther. 2011;10(1):126–137. doi:10.1158/1535-7163.MCT-10-0574.
  55. Kataoka Y, Mukohara T, Tomioka H, et al. Foretinib (GSK1363089), a multi-kinase inhibitor of MET and VEGFRs, inhibits growth of gastric cancer cell lines by blocking inter-receptor tyrosine kinase networks. Invest New Drugs. 2012;30(4):1352–1360. doi:10.1007/s10637-011-9699-0.
  56. Glen H, Mason S, Patel H, Macleod K, Brunton VG. E7080, a multi-targeted tyrosine kinase inhibitor suppresses tumor cell migration and invasion. BMC Cancer. 2011;11(1):309. doi:10.1186/1471-2407-11-309.
  57. Zhou Y, Chen Y, Tong L, et al. AL3810, a multi-tyrosine kinase inhibitor, exhibits potent anti-angiogenic and anti-tumour activity via targeting VEGFR, FGFR and PDGFR. J Cell Mol Med. 2012;16(10):2321–2330. doi:10.1111/j.1582-4934.2012.01541.x.
  58. Chen J, Deangelo DJ, Kutok JL, et al. PKC412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion tyrosine kinase and is active in treatment of stem cell myeloproliferative disorder. Proc Natl Acad Sci USA. 2004;101(40):14479–14484. doi:10.1073/pnas.0404438101.
  59. Török S, Cserepes T M, Rényi-Vámos F, Döme B. [Nintedanib (BIBF 1120) in the treatment of solid cancers: an overview of biological and clinical aspects]. Magy Onkol. 2012;56(3):199–208.
  60. Guagnano V, Kauffmann A, Wöhrle S, et al. FGFR genetic alterations predict for sensitivity to NVP-BGJ398, a selective pan-FGFR inhibitor. Cancer Discov. 2012;2(12):1118–1133. doi:10.1158/2159-8290.CD-12-0210.
  61. Guagnano V, Furet P, Spanka C, et al. Discovery of 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), a potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinase. J Med Chem. 2011;54(20):7066–7083. doi:10.1021/jm2006222.
  62. Laird AD, Christensen JG, Li G, et al. SU6668 inhibits Flk-1/KDR and PDGFRbeta in vivo, resulting in rapid apoptosis of tumor vasculature and tumor regression in mice. FASEB J. 2002;16(7):681–690. doi:10.1096/fj.01-0700com.
  63. Liao RG, Jung J, Tchaicha J, et al. Inhibitor-sensitive FGFR2 and FGFR3 mutations in lung squamous cell carcinoma. Cancer Res. 2013;73(16):5195–5205. doi:10.1158/0008-5472.CAN-12-3950.
  64. de Brito LR, Batey MA, Zhao Y, et al. Comparative pre-clinical evaluation of receptor tyrosine kinase inhibitors for the treatment of multiple myeloma. Leuk Res. 2011;35(9):1233–1240. doi:10.1016/j.leukres.2011.01.011.
  65. Gozgit JM, Wong MJ, Moran L, et al. Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer models. Mol Cancer Ther. 2012;11(3):690–699. doi:10.1158/1535-7163.MCT-11-0450.
  66. Ettrich TJ, Seufferlein T. Regorafenib. Recent Results Cancer Res. 2014;201(Chapter 10):185–196. doi:10.1007/978-3-642-54490-3_10.

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