A single primary cilium projects from most vertebrate cells to guide cell fate decisions. A growing list of signaling molecules is found to function through cilia and control ciliogenesis, including the fibroblast growth factor receptors (FGFR). Aberrant FGFR activity produces abnormal cilia with deregulated signaling, which contributes to pathogenesis of the FGFR-mediated genetic disorders. FGFR lesions are also found in cancer, raising a possibility of cilia involvement in the neoplastic transformation and tumor progression. Here, we focus on FGFR gene fusions, and discuss the possible mechanisms by which they function as oncogenic drivers. We show that a substantial portion of the FGFR fusion partners are proteins associated with the centrosome cycle, including organization of the mitotic spindle and ciliogenesis. The functions of centrosome proteins are often lost with the gene fusion, leading to haploinsufficiency that induces cilia loss and deregulated cell division. We speculate that this complements the ectopic FGFR activity and drives the FGFR fusion cancers.

Department of Biology Faculty of Medicine Masaryk University 62500 Brno Czech Republic

Institute of Animal Physiology and Genetics of the CAS 60200 Brno Czech Republic

International Clinical Research Center St Anne's University Hospital 65691 Brno Czech Republic

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Reiter J.F., Leroux M.R. Genes and molecular pathways underpinning ciliopathies. Nat. Rev. Mol. Cell Biol. 2017;18:533–547. doi: 10.1038/nrm.2017.60. PubMed DOI PMC

Kopinke D., Norris A.M., Mukhopadhyay S. Developmental and regenerative paradigms of cilia regulated hedgehog signaling. Semin. Cell Dev. Biol. 2021;110:89–103. doi: 10.1016/j.semcdb.2020.05.029. PubMed DOI PMC

Ford M.J., Yeyati P.L., Mali G.R., Keighren M.A., Waddell S.H., Mjoseng H.K., Douglas A.T., Hall E.A., Sakaue-Sawano A., Miyawaki A., et al. A Cell/Cilia Cycle Biosensor for Single-Cell Kinetics Reveals Persistence of Cilia after G1/S Transition Is a General Property in Cells and Mice. Dev. Cell. 2018;47:509–523.e5. doi: 10.1016/j.devcel.2018.10.027. PubMed DOI PMC

Paridaen J.T.M.L., Wilsch-Bräuninger M., Huttner W.B. Asymmetric Inheritance of Centrosome-Associated Primary Cilium Membrane Directs Ciliogenesis after Cell Division. Cell. 2013;155:333–344. doi: 10.1016/j.cell.2013.08.060. PubMed DOI

Plotnikova O.V., Pugacheva E.N., Golemis E.A. Primary Cilia and the Cell Cycle. 1st ed. Volume 94. Elsevier; Amsterdam, The Netherlands: 2009. PubMed PMC

Ke Y.-N., Yang W.-X. Primary cilium: An elaborate structure that blocks cell division? Gene. 2014;547:175–185. doi: 10.1016/j.gene.2014.06.050. PubMed DOI

Pugacheva E.N., Jablonski S.A., Hartman T.R., Henske E.P., Golemis E.A. HEF1-Dependent Aurora A Activation Induces Disassembly of the Primary Cilium. Cell. 2007;129:1351–1363. doi: 10.1016/j.cell.2007.04.035. PubMed DOI PMC

Inoko A., Matsuyama M., Goto H., Ohmuro-Matsuyama Y., Hayashi Y., Enomoto M., Ibi M., Urano T., Yonemura S., Kiyono T., et al. Trichoplein and Aurora A block aberrant primary cilia assembly in proliferating cells. J. Cell Biol. 2012;197:391–405. doi: 10.1083/jcb.201106101. PubMed DOI PMC

Wang G., Chen Q., Zhang X., Zhang B., Zhuo X., Liu J., Jiang Q., Zhang C. PCM1 recruits Plk1 to the pericentriolar matrix to promote primary cilia disassembly before mitotic entry. J. Cell Sci. 2013;126:1355–1365. doi: 10.1242/jcs.114918. PubMed DOI

Cappello P., Blaser H., Gorrini C., Lin D.C.C., Elia A.J., Wakeham A., Haider S., Boutros P.C., Mason J.M., Miller N.A., et al. Role of Nek2 on centrosome duplication and aneuploidy in breast cancer cells. Oncogene. 2014;33:2375–2384. doi: 10.1038/onc.2013.183. PubMed DOI

Dere R., Perkins A.L., Bawa-Khalfe T., Jonasch D., Walker C.L. β-Catenin links von Hippel-Lindau to Aurora kinase A and loss of primary cilia in renal cell carcinoma. J. Am. Soc. Nephrol. 2015;26:553–564. doi: 10.1681/ASN.2013090984. PubMed DOI PMC

Egeberg D.L., Lethan M., Manguso R., Schneider L., Awan A., Jørgensen T.S., Byskov A.G., Pedersen L.B., Christensen S.T. Primary cilia and aberrant cell signaling in epithelial ovarian cancer. Cilia. 2012;1:15. doi: 10.1186/2046-2530-1-15. PubMed DOI PMC

Sarkisian M.R., Li W., Di Cunto F., D’Mello S.R., LoTurco J.J. Citron-kinase, a protein essential to cytokinesis in neuronal progenitors, is deleted in the flathead mutant rat. J. Neurosci. 2002;22:1–5. doi: 10.1523/JNEUROSCI.22-08-j0001.2002. PubMed DOI PMC

Miyamoto T., Hosoba K., Ochiai H., Royba E., Izumi H., Sakuma T., Yamamoto T., Dynlacht B.D., Matsuura S. The Microtubule-Depolymerizing activity of a mitotic kinesin protein KIF2A drives primary cilia disassembly coupled with cell proliferation. Cell Rep. 2015;10:664–673. doi: 10.1016/j.celrep.2015.01.003. PubMed DOI PMC

Michaud E.J., Yoder B.K. The primary cilium in cell signaling and cancer. Cancer Res. 2006;66:6463–6467. doi: 10.1158/0008-5472.CAN-06-0462. PubMed DOI

Frett B., Brown R.V., Ma M., Hu W., Han H., Li H.Y. Therapeutic melting pot of never in mitosis gene a related kinase 2 (Nek2): A perspective on Nek2 as an oncology target and recent advancements in Nek2 small molecule inhibition. J. Med. Chem. 2014;57:5835–5844. doi: 10.1021/jm401719n. PubMed DOI PMC

Gradilone S.A., Habringer S., Masyuk T.V., Howard B.N., Masyuk A.I., Larusso N.F. HDAC6 is overexpressed in cystic cholangiocytes and its inhibition reduces cystogenesis. Am. J. Pathol. 2014;184:600–608. doi: 10.1016/j.ajpath.2013.11.027. PubMed DOI PMC

Lorenzo Pisarello M., Masyuk T.V., Gradilone S.A., Masyuk A.I., Ding J.F., Lee P.Y., LaRusso N.F. Combination of a Histone Deacetylase 6 Inhibitor and a Somatostatin Receptor Agonist Synergistically Reduces Hepatorenal Cystogenesis in an Animal Model of Polycystic Liver Disease. Am. J. Pathol. 2018;188:981–994. doi: 10.1016/j.ajpath.2017.12.016. PubMed DOI PMC

Sarkisian M.R., Siebzehnrubl D., Hoang-Minh L., Deleyrolle L., Silver D.J., Siebzehnrubl F.A., Guadiana S.M., Srivinasan G., Semple-Rowland S., Harrison J.K., et al. Detection of primary cilia in human glioblastoma. J. Neurooncol. 2014;117:15–24. doi: 10.1007/s11060-013-1340-y. PubMed DOI PMC

Gradilone S.A., Radtke B.N., Bogert P.S., Huang B.Q., Gajdos G.B., LaRusso N.F. HDAC6 inhibition restores ciliary expression and decreases tumor growth. Cancer Res. 2013;73:2259–2270. doi: 10.1158/0008-5472.CAN-12-2938. PubMed DOI PMC

Xiang W., Guo F., Cheng W., Zhang J., Huang J., Wang R., Ma Z., Xu K. HDAC6 inhibition suppresses chondrosarcoma by restoring the expression of primary cilia. Oncol. Rep. 2017;38:229–236. doi: 10.3892/or.2017.5694. PubMed DOI

Higgins M., Obaidi I., McMorrow T. Primary cilia and their role in cancer (Review) Oncol. Lett. 2019;17:3041–3047. doi: 10.3892/ol.2019.9942. PubMed DOI PMC

Peixoto E., Richard S., Pant K., Biswas A., Gradilone S.A. The primary cilium: Its role as a tumor suppressor organelle. Biochem. Pharmacol. 2020;175:113906. doi: 10.1016/j.bcp.2020.113906. PubMed DOI PMC

Kiseleva A.A., Nikonova A.S., Golemis E.A. Patterns of Ciliation and Ciliary Signaling in Cancer. Rev. Physiol. Biochem. Pharmacol. 2020 doi: 10.1007/112_2020_36. PubMed DOI PMC

Sabanovic B., Giulietti M., Piva F. Role of primary cilium in pancreatic ductal adenocarcinoma (Review) Int. J. Oncol. 2020;57:1095–1102. doi: 10.3892/ijo.2020.5121. PubMed DOI

Moser J.J., Fritzler M.J., Rattner J.B. Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells. BMC Cancer. 2009;9:1–12. doi: 10.1186/1471-2407-9-448. PubMed DOI PMC

Seeley E.S., Carrière C., Goetze T., Longnecker D.S., Korc M. Pancreatic cancer and precursor pancreatic intraepithelial neoplasia lesions are devoid of primary cilia. Cancer Res. 2009;69:422–430. doi: 10.1158/0008-5472.CAN-08-1290. PubMed DOI PMC

Tian H., Callahan C.A., Dupree K.J., Darbonne W.C., Ahn C.P., Scales S.J., De Sauvage F.J. Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis. Proc. Natl. Acad. Sci. USA. 2009;106:4254–4259. doi: 10.1073/pnas.0813203106. PubMed DOI PMC

Yuan K., Frolova N., Xie Y., Wang D., Cook L., Kwon Y.J., Steg A.D., Serra R., Frost A.R. Primary cilia are decreased in breast cancer: Analysis of a collection of human breast cancer cell lines and tissues. J. Histochem. Cytochem. 2010;58:857–870. doi: 10.1369/jhc.2010.955856. PubMed DOI PMC

Nobutani K., Shimono Y., Yoshida M., Mizutani K., Minami A., Kono S., Mukohara T., Yamasaki T., Itoh T., Takao S., et al. Absence of primary cilia in cell cycle-arrested human breast cancer cells. Genes Cells. 2014;19:141–152. doi: 10.1111/gtc.12122. PubMed DOI

Menzl I., Lebeau L., Pandey R., Hassounah N.B., Li F.W., Nagle R., Weihs K., McDermott K.M. Loss of primary cilia occurs early in breast cancer development. Cilia. 2014;3:7. doi: 10.1186/2046-2530-3-7. PubMed DOI PMC

Hassounah N.B., Nunez M., Fordyce C., Roe D., Nagle R., Bunch T., McDermott K.M. Inhibition of ciliogenesis promotes Hedgehog signaling, tumorigenesis, and metastasis in breast cancer. Mol. Cancer Res. 2017;15:1421–1430. doi: 10.1158/1541-7786.MCR-17-0034. PubMed DOI PMC

Hassounah N.B., Nagle R., Saboda K., Roe D.J., Dalkin B.L., McDermott K.M. Primary Cilia Are Lost in Preinvasive and Invasive Prostate Cancer. PLoS ONE. 2013;8:e68521. doi: 10.1371/journal.pone.0068521. PubMed DOI PMC

Fu W., Asp P., Canter B., Dynlacht B.D. Primary cilia control hedgehog signaling during muscle differentiation and are deregulated in rhabdomyosarcoma. Proc. Natl. Acad. Sci. USA. 2014;111:9151–9156. doi: 10.1073/pnas.1323265111. PubMed DOI PMC

Ho L., Ali S.A., Al-Jazrawe M., Kandel R., Wunder J.S., Alman B.A. Primary cilia attenuate hedgehog signalling in neoplastic chondrocytes. Oncogene. 2013;32:5388–5396. doi: 10.1038/onc.2012.588. PubMed DOI PMC

Jackman W.R., Yoo J.J., Stock D.W. Hedgehog signaling is required at multiple stages of zebrafish tooth development. BMC Dev. Biol. 2010;10 doi: 10.1186/1471-213X-10-119. PubMed DOI PMC

Cobourne M.T., Sharpe P.T. Sonic Hedgehog Signaling and the Developing Tooth. Curr. Top. Dev. Biol. 2004;65:255–287. doi: 10.1016/S0070-2153(04)65010-1. PubMed DOI

Rallis A., Navarro J.A., Rass M., Hu A., Birman S., Schneuwly S., Thérond P.P. Hedgehog Signaling Modulates Glial Proteostasis and Lifespan. Cell Rep. 2020;30:2627–2643.e5. doi: 10.1016/j.celrep.2020.02.006. PubMed DOI

Petrova R., Joyner A.L. Roles for Hedgehog signaling in adult organ homeostasis and repair. Development. 2014;141:3445–3457. doi: 10.1242/dev.083691. PubMed DOI PMC

Büller N.V.J.A., Rosekrans S.L., Westerlund J., van den Brink G.R. Hedgehog signaling and maintenance of homeostasis in the intestinal epithelium. Physiology. 2012;27:148–155. doi: 10.1152/physiol.00003.2012. PubMed DOI

Heemskerk J., DiNardo S. Drosophila hedgehog acts as a morphogen in cellular patterning. Cell. 1994;76:449–460. doi: 10.1016/0092-8674(94)90110-4. PubMed DOI

Chapouly C., Guimbal S., Hollier P.L., Renault M.A. Role of hedgehog signaling in vasculature development, differentiation, and maintenance. Int. J. Mol. Sci. 2019;20:3076. doi: 10.3390/ijms20123076. PubMed DOI PMC

Ehlen H.W.A., Buelens L.A., Vortkamp A. Hedgehog signaling in skeletal develoment. Birth Defects Res. Part C Embryo Today Rev. 2006;78:267–279. doi: 10.1002/bdrc.20076. PubMed DOI

Hebrok M. Hedgehog signaling in pancreas development. Mech. Dev. 2003;120:45–57. doi: 10.1016/S0925-4773(02)00331-3. PubMed DOI

Katoh Y., Katoh M. Hedgehog Target Genes: Mechanisms of Carcinogenesis Induced by Aberrant Hedgehog Signaling Activation. Curr. Mol. Med. 2009;9:873–886. doi: 10.2174/156652409789105570. PubMed DOI

Jeng K.S., Chang C.F., Lin S.S. Sonic hedgehog signaling in organogenesis, tumors, and tumor microenvironments. Int. J. Mol. Sci. 2020;21:758. doi: 10.3390/ijms21030758. PubMed DOI PMC

Haycraft C.J., Banizs B., Aydin-Son Y., Zhang Q., Michaud E.J., Yoder B.K. Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function. PLoS Genet. 2005;1:e10053. doi: 10.1371/journal.pgen.0010053. PubMed DOI PMC

Tukachinsky H., Lopez L.V., Salic A. A mechanism for vertebrate Hedgehog signaling: Recruitment to cilia and dissociation of SuFu-Gli protein complexes. J. Cell Biol. 2010;191:415–428. doi: 10.1083/jcb.201004108. PubMed DOI PMC

Dai P., Akimaru H., Tanaka Y., Maekawa T., Nakafuku M., Ishii S. Sonic hedgehog-induced activation of the Gli1 promoter is mediated by GLI3. J. Biol. Chem. 1999;274:8143–8152. doi: 10.1074/jbc.274.12.8143. PubMed DOI

Su Y., Ospina J.K., Zhang J., Michelson A.P., Schoen A.M., Zhu A.J. Sequential phosphorylation of smoothened transduces graded hedgehog signaling. Sci. Signal. 2011;4:1–15. doi: 10.1126/scisignal.2001747. PubMed DOI PMC

Rohatgi R., Milenkovic L., Scott M.P. Patched1 Regulates Hedgehog Signaling at the Primary Cilium. Science. 2007;317:372–376. doi: 10.1126/science.1139740. PubMed DOI

Han Y.G., Kim H.J., Dlugosz A.A., Ellison D.W., Gilbertson R.J., Alvarez-Buylla A. Dual and opposing roles of primary cilia in medulloblastoma development. Nat. Med. 2009;15:1062–1065. doi: 10.1038/nm.2020. PubMed DOI PMC

Barakat M.T., Humke E.W., Scott M.P. Kif3a is necessary for initiation and maintenance of medulloblastoma. Carcinogenesis. 2013;34:1382–1392. doi: 10.1093/carcin/bgt041. PubMed DOI PMC

Wong S.Y., Seol A.D., So P.-L., Ermilov A.N., Bichakjian C.K., Epstein E.H., Dlugosz A.A., Reiter J.F. Primary cilia can both mediate and suppress Hedgehog pathway–dependent tumorigenesis. Nat. Med. 2009;15:1055–1061. doi: 10.1038/nm.2011. PubMed DOI PMC

Li L., Grausam K.B., Wang J., Lun M.P., Ohli J., Lidov H.G.W., Calicchio M.L., Zeng E., Salisbury J.L., Wechsler-Reya R.J., et al. Sonic Hedgehog promotes proliferation of Notch-dependent monociliated choroid plexus tumour cells. Nat. Cell Biol. 2016;18:418–430. doi: 10.1038/ncb3327. PubMed DOI PMC

Guen V.J., Chavarria T.E., Kröger C., Ye X., Weinberg R.A., Lees J.A. EMT programs promote basal mammary stem cell and tumor-initiating cell stemness by inducing primary ciliogenesis and Hedgehog signaling. Proc. Natl. Acad. Sci. USA. 2017;114:E10532–E10539. doi: 10.1073/pnas.1711534114. PubMed DOI PMC

Lee P.L., Johnson D.E., Cousens L.S., Fried V.A., Williams L.T. Purification and complementary DNA cloning of a receptor for basic fibroblast growth factor. Science. 1989;245:57–60. doi: 10.1126/science.2544996. PubMed DOI

Kornbluth S., Paulson K.E., Hanafusa H. Novel tyrosine kinase identified by phosphotyrosine antibody screening of cDNA libraries. Mol. Cell. Biol. 1988;8:5541–5544. doi: 10.1128/MCB.8.12.5541. PubMed DOI PMC

Keegan K., Johnson D.E., Williams L.T., Hayman M.J. Isolation of an additional member of the fibroblast growth factor receptor family, FGFR-3. Proc. Natl. Acad. Sci. USA. 1991;88:1095–1099. doi: 10.1073/pnas.88.4.1095. PubMed DOI PMC

Partanen J., Makela T.P., Eerola E., Korhonen J., Hirvonen H., Claesson-Welsh L., Alitalo K. FGFR-4, a novel acidic fibroblast growth factor receptor with a distinct expression pattern. EMBO J. 1991;10:1347–1354. doi: 10.1002/j.1460-2075.1991.tb07654.x. PubMed DOI PMC

Ornitz D.M., Xu J., Colvin J.S., McEwen D.G., MacArthur C.A., Coulier F., Gao G., Goldfarb M. Receptor specificity of the fibroblast growth factor family. J. Biol. Chem. 1996;271:15292–15297. doi: 10.1074/jbc.271.25.15292. PubMed DOI

Ornitz D.M., Itoh N. Fibroblast growth factors. Genome Biol. 2001;2:reviews3005.1. doi: 10.1186/gb-2001-2-3-reviews3005. PubMed DOI PMC

Ornitz D.M., Marie P.J. Fibroblast growth factor signaling in skeletal development and disease. Genes Dev. 2015;29:1463–1486. doi: 10.1101/gad.266551.115. PubMed DOI PMC

Turner N., Grose R. Fibroblast growth factor signalling: From development to cancer. Nat. Rev. Cancer. 2010;10:116–129. doi: 10.1038/nrc2780. PubMed DOI

Plotnikov A.N., Schlessinger J., Hubbard S.R., Mohammadi M. Structural Basis for FGF Receptor Dimerization and Activation et al Dimerization of the extracellular domains leads to juxtaposition of the cytoplasmic domains and. Cell. 1999;98:641–650. doi: 10.1016/S0092-8674(00)80051-3. PubMed DOI

Eswarakumar V.P., Lax I., Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005;16:139–149. doi: 10.1016/j.cytogfr.2005.01.001. PubMed DOI

Schlessinger J., Plotnikov A.N., Ibrahimi O.A., Eliseenkova A.V., Yeh B.K., Yayon A., Linhardt R.J., Mohammadi M. Crystal Structure of a Ternary FGF-FGFR-Heparin Complex Reveals a Dual Role for Heparin in FGFR Binding and Dimerization. Mol. Cell. 2000;6:743–750. doi: 10.1016/S1097-2765(00)00073-3. PubMed DOI

Luo Y., Ye S., Kan M., McKeehan W.L. Control of Fibroblast Growth Factor (FGF) 7- and FGF1-induced mitogenesis and downstream signaling by distinct heparin octasaccharide motifs. J. Biol. Chem. 2006;281:21052–21061. doi: 10.1074/jbc.M601559200. PubMed DOI

Goetz R., Beenken A., Ibrahimi O.A., Kalinina J., Olsen S.K., Eliseenkova A.V., Xu C., Neubert T.A., Zhang F., Linhardt R.J., et al. Molecular Insights into the Klotho-Dependent, Endocrine Mode of Action of Fibroblast Growth Factor 19 Subfamily Members. Mol. Cell. Biol. 2007;27:3417–3428. doi: 10.1128/MCB.02249-06. PubMed DOI PMC

Goetz R., Ohnishi M., Ding X., Kurosu H., Wang L., Akiyoshi J., Ma J., Gai W., Sidis Y., Pitteloud N., et al. Klotho Coreceptors Inhibit Signaling by Paracrine Fibroblast Growth Factor 8 Subfamily Ligands. Mol. Cell. Biol. 2012;32:1944–1954. doi: 10.1128/MCB.06603-11. PubMed DOI PMC

Lin B.C., Wang M., Blackmore C., Desnoyers L.R. Liver-specific activities of FGF19 require klotho beta. J. Biol. Chem. 2007;282:27277–27284. doi: 10.1074/jbc.M704244200. PubMed DOI

Quarto N., Amalric F. Heparan sulfate proteoglycans as transducers of FGF-2 signalling. J. Cell Sci. 1994;107:3201–3212. doi: 10.1242/jcs.107.11.3201. PubMed DOI

Zhang Z., Coomans C., David G. Membrane heparan sulfate proteoglycan-supported FGF2-FGFR1 signaling: Evidence in support of the “cooperative end structures” model. J. Biol. Chem. 2001;276:41921–41929. doi: 10.1074/jbc.M106608200. PubMed DOI

Ornitz D.M., Yayon A., Flanagan J.G., Svahn C.M., Levi E., Leder P. Heparin is required for cell-free binding of basic fibroblast growth factor to a soluble receptor and for mitogenesis in whole cells. Mol. Cell. Biol. 1992;12:240–247. doi: 10.1128/MCB.12.1.240. PubMed DOI PMC

Spivak-Kroizman T., Lemmon M.A., Dikic I., Ladbury J.E., Pinchasi D., Huang J., Jaye M., Crumley G., Schlessinger J., Lax I. Heparin-induced oligomerization of FGF molecules is responsible for FGF receptor dimerization, activation, and cell proliferation. Cell. 1994;79:1015–1024. doi: 10.1016/0092-8674(94)90032-9. PubMed DOI

Rapraeger A.C., Krufka A., Olwin B.B. Requirement of heparan sulfate for bFGF-mediated fibroblast growth and myoblast differentiation. Science. 1991;252:1705–1708. doi: 10.1126/science.1646484. PubMed DOI

Kuro-o M. The Klotho proteins in health and disease. Nat. Rev. Nephrol. 2019;15:27–44. doi: 10.1038/s41581-018-0078-3. PubMed DOI

Hu M.C., Shiizaki K., Kuro-O M., Moe O.W. Fibroblast growth factor 23 and klotho: Physiology and pathophysiology of an endocrine network of mineral metabolism. Annu. Rev. Physiol. 2013;75:503–533. doi: 10.1146/annurev-physiol-030212-183727. PubMed DOI PMC

Tacer K.F., Bookout A.L., Ding X., Kurosu H., John G.B., Wang L., Goetz R., Mohammadi M., Kuro-o M., Mangelsdorf D.J., et al. Research resource: Comprehensive expression atlas of the fibroblast growth factor system in adult mouse. Mol. Endocrinol. 2010;24:2050–2064. doi: 10.1210/me.2010-0142. PubMed DOI PMC

Arman E., Haffner-Krausz R., Gorivodsky M., Lonai P. Fgfr2 is required for limb outgrowth and lung-branching morphogenesis. Proc. Natl. Acad. Sci. USA. 1999;96:11895–11899. doi: 10.1073/pnas.96.21.11895. PubMed DOI PMC

Danopoulos S., Thornton M.E., Grubbs B.H., Frey M.R., Warburton D., Bellusci S., Al Alam D. Discordant roles for FGF ligands in lung branching morphogenesis between human and mouse. J. Pathol. 2019;247:254–265. doi: 10.1002/path.5188. PubMed DOI PMC

McDougall K., Kubu C., Verdi J.M., Meakin S.O. Developmental expression patterns of the signaling adapters FRS-2 and FRS-3 during early embryogenesis. Mech. Dev. 2001;103:145–148. doi: 10.1016/S0925-4773(01)00337-9. PubMed DOI

Weinstein M., Xu X., Ohyama K., Deng C.X. FGFR-3 and FGFR-4 function cooperatively to direct alveogenesis in the murine lung. Development. 1998;125:3615–3623. doi: 10.1242/dev.125.18.3615. PubMed DOI

Dudley A.T., Godin R.E., Robertson E.J. Interaction between FGF and BMP signaling pathways regulates development of metanephric mesenchyme. Genes Dev. 1999;13:1601–1613. doi: 10.1101/gad.13.12.1601. PubMed DOI PMC

Kastner S., Elias M.C., Rivera A.J., Yablonka-Reuveni Z. Gene expression patterns of the fibroblast growth factors and their receptors during myogenesis of rat satellite cells. J. Histochem. Cytochem. 2000;48:1079–1096. doi: 10.1177/002215540004800805. PubMed DOI

Walker K.A., Sims-Lucas S., Bates C.M. Fibroblast growth factor receptor signaling in kidney and lower urinary tract development. Pediatr. Nephrol. 2016;31:885–895. doi: 10.1007/s00467-015-3151-1. PubMed DOI PMC

Colvin J.S., Bohne B.A., Harding G.W., McEwen D.G., Ornitz D.M. Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3. Nat. Genet. 1996;12:390–397. doi: 10.1038/ng0496-390. PubMed DOI

Shimada T., Kakitani M., Yamazaki Y., Hasegawa H., Takeuchi Y., Fujita T., Fukumoto S., Tomizuka K., Yamashita T. Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J. Clin. Invest. 2004;113:561–568. doi: 10.1172/JCI200419081. PubMed DOI PMC

Zhou M., Luo J., Chen M., Yang H., Learned R.M., DePaoli A.M., Tian H., Ling L. Mouse species-specific control of hepatocarcinogenesis and metabolism by FGF19/FGF15. J. Hepatol. 2017;66:1182–1192. doi: 10.1016/j.jhep.2017.01.027. PubMed DOI

Tomlinson E., Fu L., John L., Hultgren B., Huang X., Renz M., Stephan J.P., Tsai S.P., Powell-Braxton L., French D., et al. Transgenic mice expressing human fibroblast growth factor-19 display increased metabolic rate and decreased adiposity. Endocrinology. 2002;143:1741–1747. doi: 10.1210/endo.143.5.8850. PubMed DOI

Potthoff M.J., Boney-Montoya J., Choi M., He T., Sunny N.E., Satapati S., Suino-Powell K., Xu H.E., Gerard R.D., Finck B.N., et al. FGF15/19 regulates hepatic glucose metabolism by inhibiting the CREB-PGC-1α pathway. Cell Metab. 2011;13:729–738. doi: 10.1016/j.cmet.2011.03.019. PubMed DOI PMC

Quarles L.D. Skeletal secretion of FGF-23 regulates phosphate and vitamin D metabolism. Nat. Rev. Endocrinol. 2012;8:276–286. doi: 10.1038/nrendo.2011.218. PubMed DOI PMC

Xie Y., Su N., Yang J., Tan Q., Huang S., Jin M., Ni Z., Zhang B., Zhang D., Luo F., et al. FGF/FGFR signaling in health and disease. Signal Transduct. Target. Ther. 2020;5 doi: 10.1038/s41392-020-00222-7. PubMed DOI PMC

Floss T., Arnold H.H., Braun T. A role for FGF-6 in skeletal muscle regeneration. Genes Dev. 1997;11:2040–2051. doi: 10.1101/gad.11.16.2040. PubMed DOI PMC

Schmid G.J., Kobayashi C., Sandell L.J., Ornitz D.M. Fibroblast growth factor expression during skeletal fracture healing in mice. Dev. Dyn. 2009;238:766–774. doi: 10.1002/dvdy.21882. PubMed DOI PMC

Nakajima A., Nakajima F., Shimizu S., Ogasawara A., Wanaka A., Moriya H., Einhorn T.A., Yamazaki M. Spatial and temporal gene expression for fibroblast growth factor type I receptor (FGFR1) during fracture healing in the rat. Bone. 2001;29:458–466. doi: 10.1016/S8756-3282(01)00604-4. PubMed DOI

Goebel S., Lienau J., Rammoser U., Seefried L., Wintgens K.F., Seufert J., Duda G., Jakob F., Ebert R. FGF23 is a putative marker for bone healing and regeneration. J. Orthop. Res. 2009;27:1141–1146. doi: 10.1002/jor.20857. PubMed DOI

Hurley M.M., Adams D.J., Wang L., Jiang X., Burt P.M., Du E., Xiao L. Accelerated fracture healing in transgenic mice overexpressing an anabolic isoform of fibroblast growth factor 2. J. Cell. Biochem. 2016;117:599–611. doi: 10.1002/jcb.25308. PubMed DOI

Kunova Bosakova M., Varecha M., Hampl M., Duran I., Nita A., Buchtova M., Dosedelova H., Machat R., Xie Y., Ni Z., et al. Regulation of ciliary function by fibroblast growth factor signaling identifies FGFR3-related disorders achondroplasia and thanatophoric dysplasia as ciliopathies. Hum. Mol. Genet. 2018;27:1093–1105. doi: 10.1093/hmg/ddy031. PubMed DOI PMC

Martin L., Kaci N., Estibals V., Goudin N., Garfa-Traore M., Benoist-Lasselin C., Dambroise E., Legeai-Mallet L. Constitutively-active FGFR3 disrupts primary cilium length and IFT20 trafficking in various chondrocyte models of achondroplasia. Hum. Mol. Genet. 2018;27:1–13. doi: 10.1093/hmg/ddx374. PubMed DOI

Kunova Bosakova M., Nita A., Gregor T., Varecha M., Gudernova I., Fafilek B., Barta T., Basheer N., Abraham S.P., Balek L., et al. Fibroblast growth factor receptor influences primary cilium length through an interaction with intestinal cell kinase. Proc. Natl. Acad. Sci. USA. 2019;116:4316–4325. doi: 10.1073/pnas.1800338116. PubMed DOI PMC

Katoh M., Nakagama H. FGF Receptors: Cancer Biology and Therapeutics. Med. Res. Rev. 2014;34:280–300. doi: 10.1002/med.21288. PubMed DOI

Katoh M. Fibroblast growth factor receptors as treatment targets in clinical oncology. Nat. Rev. Clin. Oncol. 2019;16:105–122. doi: 10.1038/s41571-018-0115-y. PubMed DOI

Dutt A., Salvesen H.B., Chen T.H., Ramos A.H., Onofrio R.C., Hatton C., Nicoletti R., Winckler W., Grewal R., Hanna M., et al. Drug-sensitive FGFR2 mutations in endometrial carcinoma. Proc. Natl. Acad. Sci. USA. 2008;105:8713–8717. doi: 10.1073/pnas.0803379105. PubMed DOI PMC

Thomas A., Lee J.H., Abdullaev Z., Park K.S., Pineda M., Saidkhodjaeva L., Miettinen M., Wang Y., Pack S.D., Giaccone G. Characterization of fibroblast growth factor receptor 1 in small-cell lung cancer. J. Thorac. Oncol. 2014;9:567–571. doi: 10.1097/JTO.0000000000000089. PubMed DOI PMC

Rosty C., Aubriot M.H., Cappellen D., Bourdin J., Cartier I., Thiery J.P., Sastre-Garau X., Radvanyi F. Clinical and biological characteristics of cervical neoplasias with FGFR3 mutation. Mol. Cancer. 2005;4:2–9. doi: 10.1186/1476-4598-4-15. PubMed DOI PMC

Neugebauer J.M., Amack J.D., Peterson A.G., Bisgrove B.W., Yost H.J. FGF signalling during embryo development regulates cilia length in diverse epithelia. Nature. 2009;458:651–654. doi: 10.1038/nature07753. PubMed DOI PMC

Essner J.J., Amack J.D., Nyholm M.K., Harris E.B., Yost H.J. Kupffer’s vesicle is a ciliated organ of asymmetry in the zebrafish embryo that initiates left-right development of the brain, heart and gut. Development. 2005;132:1247–1260. doi: 10.1242/dev.01663. PubMed DOI

Yamauchi H., Miyakawa N., Miyake A., Itoh N. Fgf4 is required for left-right patterning of visceral organs in zebrafish. Dev. Biol. 2009;332:177–185. doi: 10.1016/j.ydbio.2009.05.568. PubMed DOI

Liu D.-W.W., Hsu C.-H.H., Tsai S.-M.M., Hsiao C.-D., Wang W.-P.P. A Variant of Fibroblast Growth Factor Receptor 2 (Fgfr2) Regulates Left-Right Asymmetry in Zebrafish. PLoS ONE. 2011;6:e21793. doi: 10.1371/journal.pone.0021793. PubMed DOI PMC

Sempou E., Lakhani O.A., Amalraj S., Khokha M.K. Candidate Heterotaxy Gene FGFR4 Is Essential for Patterning of the Left-Right Organizer in Xenopus. Front. Physiol. 2018;9:1–9. doi: 10.3389/fphys.2018.01705. PubMed DOI PMC

Hong S.K., Dawid I.B. FGF-dependent left-right asymmetry patterning in zebrafish is mediated by Ier2 and Fibp1. Proc. Natl. Acad. Sci. USA. 2009;106:2230–2235. doi: 10.1073/pnas.0812880106. PubMed DOI PMC

Neugebauer J.M., Cadwallader A.B., Amack J.D., Bisgrove B.W., Joseph Yost H. Differential roles for 3-OSTs in the regulation of cilia length and motility. Development. 2013;140:3892–3902. doi: 10.1242/dev.096388. PubMed DOI PMC

Caron A., Xu X., Lin X. Wnt/β-catenin signaling directly regulates Foxj1 expression and ciliogenesis in zebrafish Kupffer’s vesicle. Development. 2012;139:514–524. doi: 10.1242/dev.071746. PubMed DOI PMC

Bonnafe E., Touka M., AitLounis A., Baas D., Barras E., Ucla C., Moreau A., Flamant F., Dubruille R., Couble P., et al. The Transcription Factor RFX3 Directs Nodal Cilium Development and Left-Right Asymmetry Specification. Mol. Cell. Biol. 2004;24:4417–4427. doi: 10.1128/MCB.24.10.4417-4427.2004. PubMed DOI PMC

Bisgrove B.W., Snarr B.S., Emrazian A., Yost H.J. Polaris and Polycystin-2 in dorsal forerunner cells and Kupffer’s vesicle are required for specification of the zebrafish left-right axis. Dev. Biol. 2005;287:274–288. doi: 10.1016/j.ydbio.2005.08.047. PubMed DOI

Honda A., Kita T., Seshadri S.V., Misaki K., Ahmed Z., Ladbury J.E., Richardson G.P., Yonemura S., Ladher R.K. FGFR1-mediated protocadherin-15 loading mediates cargo specificity during intraflagellar transport in inner ear hair-cell kinocilia. Proc. Natl. Acad. Sci. USA. 2018;115:8388–8393. doi: 10.1073/pnas.1719861115. PubMed DOI PMC

Yuan X., Liu M., Cao X., Yang S. Ciliary IFT80 regulates dental pulp stem cells differentiation by FGF/FGFR1 and Hh/BMP2 signaling. Int. J. Biol. Sci. 2019;15:2087–2099. doi: 10.7150/ijbs.27231. PubMed DOI PMC

Taylor S.P., Bosakova M.K., Varecha M., Balek L., Barta T., Trantirek L., Jelinkova I., Duran I., Vesela I., Forlenza K.N., et al. An inactivating mutation in intestinal cell kinase, ICK, impairs hedgehog signalling and causes short rib-polydactyly syndrome. Hum. Mol. Genet. 2016;25:3998–4011. doi: 10.1093/hmg/ddw240. PubMed DOI PMC

Moon H., Song J., Shin J.O., Lee H., Kim H.K., Eggenschwiller J.T., Bok J., Ko H.W. Intestinal cell kinase, aprotein associated with endocrine-cerebro-osteodysplasia syndrome is a key regulator of cilia length and Hedgehog signaling. Proc. Natl. Acad. Sci. USA. 2014;111:8541–8546. doi: 10.1073/pnas.1323161111. PubMed DOI PMC

Chaya T., Omori Y., Kuwahara R., Furukawa T. ICK is essential for cell type-specific ciliogenesis and the regulation of ciliary transport. EMBO J. 2014;33:1227–1242. doi: 10.1002/embj.201488175. PubMed DOI PMC

Tong Y., Park S.H., Wu D., Xu W., Guillot S.J., Jin L., Li X., Wang Y., Lin C.-S., Fu Z. An essential role of intestinal cell kinase in lung development is linked to the perinatal lethality of human ECO syndrome. FEBS Lett. 2017;591:1247–1257. doi: 10.1002/1873-3468.12644. PubMed DOI PMC

Ding M., Jin L., Xie L., Park S.H., Tong Y., Wu D., Chhabra A.B., Fu Z., Li X. A Murine Model for Human ECO Syndrome Reveals a Critical Role of Intestinal Cell Kinase in Skeletal Development. Calcif. Tissue Int. 2018;102:348–357. doi: 10.1007/s00223-017-0355-3. PubMed DOI PMC

Okamoto S., Chaya T., Omori Y., Kuwahara R., Kubo S., Sakaguchi H., Furukawa T. Ick ciliary kinase is essential for planar cell polarity formation in inner ear hair cells and hearing function. J. Neurosci. 2017;37:2073–2085. doi: 10.1523/JNEUROSCI.3067-16.2017. PubMed DOI PMC

Berman S.A., Wilson N.F., Haas N.A., Lefebvre P.A. A Novel MAP Kinase Regulates Flagellar Length in Chlamydomonas. Curr. Biol. 2003;13:1145–1149. doi: 10.1016/S0960-9822(03)00415-9. PubMed DOI

Burghoorn J., Dekkers M.P.J., Rademakers S., De Jong T., Willemsen R., Jansen G. Mutation of the MAP kinase DYF-5 affects docking and undocking of kinesin-2 motors and reduces their speed in the cilia of Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA. 2007;104:7157–7162. doi: 10.1073/pnas.0606974104. PubMed DOI PMC

Rousseau F., El Ghouzzi V., Delezoide A.L., Legeai-Mallet L., Le Merrer M., Munnich A., Bonaventure J. Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1) Hum. Mol. Genet. 1996;5:509–512. doi: 10.1093/hmg/5.4.509. PubMed DOI

Tavormina P.L., Shiang R., Thompson L.M., Zhu Y.Z., Wilkin D.J., Lachman R.S., Wilcox W.R., Rimoin D.L., Cohn D.H., Wasmuth J.J. Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3. Nat. Genet. 1995;9:321–328. doi: 10.1038/ng0395-321. PubMed DOI

Tavormina P.L., Rimoin D.L., Cohn D.H., Zhu Y.Z., Shiang R., Wasmuth J.J. Another mutation that results in the substitution of an unpaired cysteine residue in the extracellular domain of FGFR3 in thanatophoric dysplasia type I. Hum. Mol. Genet. 1995;4:2175–2177. doi: 10.1093/hmg/4.11.2175. PubMed DOI

Shiang R., Thompson L.M., Zhu Y.Z., Church D.M., Fielder T.J., Bocian M., Winokur S.T., Wasmuth J.J. Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell. 1994;78:335–342. doi: 10.1016/0092-8674(94)90302-6. PubMed DOI

Bellus G.A., Hefferon T.W., De Luna R.I.O., Hecht J.T., Horton W.A., Machado M., Kaitila I., McIntosh I., Francomano C.A. Achondroplasia is defined by recurrent G380R mutations of FGFR3. Am. J. Hum. Genet. 1995;56:368–373. PubMed PMC

Van Rhijn B.W.G., van Tilborg A.A.G., Lurkin I., Bonaventure J., de Vries A., Thiery J.P., van der Kwast T.H., Zwarthoff E.C. Novel fibroblast growth factor receptor 3 (FGFR3) mutations in bladder cancer previously identified in non-lethal skeletal disorders. Eur. J. Hum. Genet. 2002;10:819–824. doi: 10.1038/sj.ejhg.5200883. PubMed DOI

Gallo L.H., Nelson K.N., Meyer A.N., Donoghue D.J. Functions of Fibroblast Growth Factor Receptors in cancer defined by novel translocations and mutations. Cytokine Growth Factor Rev. 2015;26:425–449. doi: 10.1016/j.cytogfr.2015.03.003. PubMed DOI

Bernard-Pierrot I., Brams A., Dunois-Lardé C., Caillault A., Diez de Medina S.G., Cappellen D., Graff G., Thiery J.P., Chopin D., Ricol D., et al. Oncogenic properties of the mutated forms of fibroblast growth factor receptor 3b. Carcinogenesis. 2006;27:740–747. doi: 10.1093/carcin/bgi290. PubMed DOI

Greulich H., Pollock P.M. Targeting mutant fibroblast growth factor receptors in cancer. Trends Mol. Med. 2011;17:283–292. doi: 10.1016/j.molmed.2011.01.012. PubMed DOI PMC

Shinmura K., Kato H., Matsuura S., Inoue Y., Igarashi H., Nagura K., Nakamura S., Maruyama K., Tajima M., Funai K., et al. A novel somatic FGFR3 mutation in primary lung cancer. Oncol. Rep. 2014;31:1219–1224. doi: 10.3892/or.2014.2984. PubMed DOI

Naski M.C., Colvin J.S., Coffin J.D., Ornitz D.M. Repression of hedgehog signaling and BMP4 expression in growth plate cartilage by fibroblast growth factor receptor 3. Development. 1998;125:4977–4988. doi: 10.1242/dev.125.24.4977. PubMed DOI

Chen J., Chien K.R. Complexity in simplicity: Monogenic disorders and c complex cardiomyopathies. J. Clin. Invest. 1999;103:1483–1485. doi: 10.1172/JCI7297. PubMed DOI PMC

Chen L., Li C., Qiao W., Xu X., Deng C. A Ser365→Cys mutation of fibroblast growth factor receptor 3 in mouse downregulates lhh/PTHrP signals and causes severe achondroplasia. Hum. Mol. Genet. 2001;10:457–465. doi: 10.1093/hmg/10.5.457. PubMed DOI

Wren K.N., Craft J.M., Tritschler D., Schauer A., Patel D.K., Smith E.F., Porter M.E., Kner P., Lechtreck K.F. A Differential Cargo-Loading Model of Ciliary Length Regulation by IFT. Curr. Biol. 2013;23:2463–2471. doi: 10.1016/j.cub.2013.10.044. PubMed DOI PMC

Zhou S., Xie Y., Tang J., Huang J., Huang Q., Xu W., Wang Z., Luo F., Wang Q., Chen H., et al. FGFR3 Deficiency Causes Multiple Chondroma-like Lesions by Upregulating Hedgehog Signaling. PLoS Genet. 2015;11:e1005214. doi: 10.1371/journal.pgen.1005214. PubMed DOI PMC

Du E., Lu C., Sheng F., Li C., Li H., Ding N., Chen Y., Zhang T., Yang K., Xu Y. Analysis of potential genes associated with primary cilia in bladder cancer. Cancer Manag. Res. 2018;10:3047–3056. doi: 10.2147/CMAR.S175419. PubMed DOI PMC

Lee K.H.S., Johmura Y., Yu L.R., Park J.E., Gao Y., Bang J.K., Zhou M., Veenstra T.D., Yeon Kim B., Lee K.H.S. Identification of a novel Wnt5a-CK1ε-Dvl2-Plk1-mediated primary cilia disassembly pathway. EMBO J. 2012;31:3104–3117. doi: 10.1038/emboj.2012.144. PubMed DOI PMC

Hsu Y.C., Kao C.Y., Chung Y.F., Lee D.C., Liu J.W., Chiu I.M. Activation of Aurora A kinase through the FGF1/FGFR signaling axis sustains the stem cell characteristics of glioblastoma cells. Exp. Cell Res. 2016;344:153–166. doi: 10.1016/j.yexcr.2016.04.012. PubMed DOI

Li X., Martinez-Ledesma E., Zhang C., Gao F., Zheng S., Ding J., Wu S., Nguyen N., Clifford S.C., Wen P.Y., et al. TIE2–FGFR1 interaction induces adaptive PI3K inhibitor resistance by upregulating Aurora A/PlK1/CDK1 signaling in glioblastoma. Cancer Res. 2019;79:5088–5101. doi: 10.1158/0008-5472.CAN-19-0325. PubMed DOI

Montaudon E., Nikitorowicz-Buniak J., Sourd L., Morisset L., El Botty R., Huguet L., Dahmani A., Painsec P., Nemati F., Vacher S., et al. PLK1 inhibition exhibits strong anti-tumoral activity in CCND1-driven breast cancer metastases with acquired palbociclib resistance. Nat. Commun. 2020;11 doi: 10.1038/s41467-020-17697-1. PubMed DOI PMC

Sánchez I., Dynlacht B.D. Cilium assembly and disassembly. Nat. Cell Biol. 2016;18:711–717. doi: 10.1038/ncb3370. PubMed DOI PMC

Werner S., Pimenta-Marques A., Bettencourt-Dias M. Maintaining centrosomes and cilia. J. Cell Sci. 2017;130:3789–3800. doi: 10.1242/jcs.203505. PubMed DOI

Wu Y.M., Su F., Kalyana-Sundaram S., Khazanov N., Ateeq B., Cao X., Lonigro R.J., Vats P., Wang R., Lin S.F., et al. Identification of targetable FGFR gene fusions in diverse cancers. Cancer Discov. 2013;3:636–647. doi: 10.1158/2159-8290.CD-13-0050. PubMed DOI PMC

L’Hôte C.G.M., Knowles M.A. Cell responses to FGFR3 signalling: Growth, differentiation and apoptosis. Exp. Cell Res. 2005;304:417–431. doi: 10.1016/j.yexcr.2004.11.012. PubMed DOI

Pepper M.S., Ferrara N., Orci L., Montesano R. Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro. Biochem. Biophys. Res. Commun. 1992;189:824–831. doi: 10.1016/0006-291X(92)92277-5. PubMed DOI

Lieu C., Heymach J., Overman M., Tran H., Kopetz S. Beyond VEGF: Inhibition of the fibroblast growth factor pathway and antiangiogenesis. Clin. Cancer Res. 2011;17:6130–6139. doi: 10.1158/1078-0432.CCR-11-0659. PubMed DOI PMC

Helsten T., Elkin S., Arthur E., Tomson B.N., Carter J., Kurzrock R. The FGFR landscape in cancer: Analysis of 4,853 tumors by next-generation sequencing. Clin. Cancer Res. 2016;22:259–267. doi: 10.1158/1078-0432.CCR-14-3212. PubMed DOI

Dienstmann R., Rodon J., Prat A., Perez-Garcia J., Adamo B., Felip E., Cortes J., Iafrate A.J., Nuciforo P., Tabernero J. Genomic aberrations in the FGFR pathway: Opportunities for targeted therapies in solid tumors. Ann. Oncol. 2014;25:552–563. doi: 10.1093/annonc/mdt419. PubMed DOI PMC

Kim S., Dubrovska A., Salamone R.J., Walker J.R., Grandinetti K.B., Bonamy G.M.C., Orth A.P., Elliott J., Porta D.G., Garcia-Echeverria C., et al. FGFR2 Promotes Breast Tumorigenicity through Maintenance of Breast Tumor-Initiating Cells. PLoS ONE. 2013;8:e51671. doi: 10.1371/journal.pone.0051671. PubMed DOI PMC

Tsimafeyeu I., Demidov L., Stepanova E., Wynn N., Ta H. Overexpression of fibroblast growth factor receptors FGFR1 and FGFR2 in renal cell carcinoma. Scand. J. Urol. Nephrol. 2011;45:190–195. doi: 10.3109/00365599.2011.552436. PubMed DOI

Giri D., Ropiquet F., Ittmann M. Alterations in expression of basic fibroblast growth factor (FGF) 2 and its receptor FGFR-1 in human prostate cancer. Clin. Cancer Res. 1999;5:1063–1071. PubMed

Di Martino E., Tomlinson D.C., Knowles M.A. A decade of FGF receptor research in bladder cancer: Past, present, and future challenges. Adv. Urol. 2012;2012 doi: 10.1155/2012/429213. PubMed DOI PMC

Byron S.A., Gartside M., Powell M.A., Wellens C.L., Gao F., Mutch D.G., Goodfellow P.J., Pollock P.M. Fgfr2 point mutations in 466 endometrioid endometrial tumors: Relationship with msi, kras, pik3ca, ctnnb1 mutations and clinicopathological features. PLoS ONE. 2012;7:e30801. doi: 10.1371/annotation/0bfaecca-0f87-43fe-97cc-f2ae3ddeb6d5. PubMed DOI PMC

Cappellen D., De Oliveira C., Ricol D., de Medina S., Bourdin J., Sastre-Garau X., Chopin D., Thiery J.P., Radvanyi F. Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. Nat. Genet. 1999;23:18–20. doi: 10.1038/12615. PubMed DOI

Ahmed Z., Schüller A.C., Suhling K., Tregidgo C., Ladbury J.E. Extracellular point mutations in FGFR2 elicit unexpected changes in intracellular signalling. Biochem. J. 2008;413:37–49. doi: 10.1042/BJ20071594. PubMed DOI

Neilson K.M., Friesel R. Ligand-independent activation of fibroblast growth factor receptors by point mutations in the extracellular, transmembrane, and kinase domains. J. Biol. Chem. 1996;271:25049–25057. doi: 10.1074/jbc.271.40.25049. PubMed DOI

Krook M.A., Reeser J.W., Ernst G., Barker H., Wilberding M., Li G., Chen H.Z., Roychowdhury S. Fibroblast growth factor receptors in cancer: Genetic alterations, diagnostics, therapeutic targets and mechanisms of resistance. Br. J. Cancer. 2021;124:880–892. doi: 10.1038/s41416-020-01157-0. PubMed DOI PMC

Ibrahimi O.A., Yeh B.K., Eliseenkova A.V., Zhang F., Olsen S.K., Igarashi M., Aaronson S.A., Linhardt R.J., Mohammadi M. Analysis of Mutations in Fibroblast Growth Factor (FGF) and a Pathogenic Mutation in FGF Receptor (FGFR) Provides Direct Evidence for the Symmetric Two-End Model for FGFR Dimerization. Mol. Cell. Biol. 2005;25:671–684. doi: 10.1128/MCB.25.2.671-684.2005. PubMed DOI PMC

Webster M.K., D’Avis P.Y., Robertson S.C., Donoghue D.J. Profound ligand-independent kinase activation of fibroblast growth factor receptor 3 by the activation loop mutation responsible for a lethal skeletal dysplasia, thanatophoric dysplasia type II. Mol. Cell. Biol. 1996;16:4081–4087. doi: 10.1128/MCB.16.8.4081. PubMed DOI PMC

Naski M.C., Wang Q., Xu J., Ornitz D.M. Graded activation of fibroblast growth factor receptor 3 by mutations causing achondroplasia and thanatophoric dysplasia. Nat. Genet. 1996;13:233–237. doi: 10.1038/ng0696-233. PubMed DOI

Bellus G.A., Bamshad M.J., Przylepa K.A., Dorst J., Lee R.R., Hurko O., Jabs E.W., Curry C.J.R., Wilcox W.R., Lachman R.S., et al. Severe achondroplasia with developmental delay and Acanthosis nigricans (SADDAN): Phenotypic analysis of a new skeletal dysplasia caused by a Lys650Met mutation in fibroblast growth factor receptor 3. Am. J. Med. Genet. 1999;85:53–65. doi: 10.1002/(SICI)1096-8628(19990702)85:1<53::AID-AJMG10>3.0.CO;2-F. PubMed DOI

Foth M., Ahmad I., Van Rhijn B.W.G., Van Der Kwast T., Bergman A.M., King L., Ridgway R., Leung H.Y., Fraser S., Sansom O.J., et al. Fibroblast growth factor receptor 3 activation plays a causative role in urothelial cancer pathogenesis in cooperation with Pten loss in mice. J. Pathol. 2014;233:148–158. doi: 10.1002/path.4334. PubMed DOI PMC

Ahmad I., Singh L.B., Foth M., Morris C.A., Taketo M.M., Wu X.R., Leung H.Y., Sansom O.J., Iwata T. K-Ras and β-catenin mutations cooperate with Fgfr3 mutations in mice to promote tumorigenesis in the skin and lung, but not in the bladder. DMM Dis. Model. Mech. 2011;4:548–555. doi: 10.1242/dmm.006874. PubMed DOI PMC

Mertens F., Johansson B., Fioretos T., Mitelman F. The emerging complexity of gene fusions in cancer. Nat. Rev. Cancer. 2015;15:371–381. doi: 10.1038/nrc3947. PubMed DOI

Schram A.M., Chang M.T., Jonsson P., Drilon A. Fusions in solid tumours: Diagnostic strategies, targeted therapy, and acquired resistance. Nat. Rev. Clin. Oncol. 2017;14:735–748. doi: 10.1038/nrclinonc.2017.127. PubMed DOI PMC

De Luca A., Abate R.E., Rachiglio A.M., Maiello M.R., Esposito C., Schettino C., Izzo F., Nasti G., Normanno N. FGFR fusions in cancer: From diagnostic approaches to therapeutic intervention. Int. J. Mol. Sci. 2020;21:6856. doi: 10.3390/ijms21186856. PubMed DOI PMC

Katoh M. FGFR inhibitors: Effects on cancer cells, tumor microenvironment and whole-body homeostasis (Review) Int. J. Mol. Med. 2016;38:3–15. doi: 10.3892/ijmm.2016.2620. PubMed DOI PMC

Wang Y., Ding X., Wang S., Moser C.D., Shaleh H.M., Mohamed E.A., Chaiteerakij R., Allotey L.K., Chen G., Miyabe K., et al. Antitumor effect of FGFR inhibitors on a novel cholangiocarcinoma patient derived xenograft mouse model endogenously expressing an FGFR2-CCDC6 fusion protein. Cancer Lett. 2016;380:163–173. doi: 10.1016/j.canlet.2016.05.017. PubMed DOI PMC

Arai Y., Totoki Y., Hosoda F., Shirota T., Hama N., Nakamura H., Ojima H., Furuta K., Shimada K., Okusaka T., et al. Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma. Hepatology. 2014;59:1427–1434. doi: 10.1002/hep.26890. PubMed DOI

Ochiai M., Yoshihara Y., Maru Y., Tetsuya M., Izumiya M., Imai T., Hippo Y. Kras-driven heterotopic tumor development from hepatobiliary organoids. Carcinogenesis. 2019 doi: 10.1093/carcin/bgz024. PubMed DOI

Sia D., Losic B., Moeini A., Cabellos L., Hao K., Revill K., Bonal D., Miltiadous O., Zhang Z., Hoshida Y., et al. Massive parallel sequencing uncovers actionable FGFR2-PPHLN1 fusion and ARAF mutations in intrahepatic cholangiocarcinoma. Nat. Commun. 2015;6 doi: 10.1038/ncomms7087. PubMed DOI

Li F., Meyer A.N., Peiris M.N., Nelson K.N., Donoghue D.J. Oncogenic fusion protein FGFR2-PPHLN1: Requirements for biological activation, and efficacy of inhibitors. Transl. Oncol. 2020;13:100853. doi: 10.1016/j.tranon.2020.100853. PubMed DOI PMC

Williams S.V., Hurst C.D., Knowles M.A. Oncogenic FGFR3 gene fusions in bladder cancer. Hum. Mol. Genet. 2013;22:795–803. doi: 10.1093/hmg/dds486. PubMed DOI PMC

Nakanishi Y., Akiyama N., Tsukaguchi T., Fujii T., Satoh Y., Ishii N., Aoki M. Mechanism of Oncogenic Signal Activation by the Novel Fusion Kinase FGFR3-BAIAP2L1. Mol. Cancer Ther. 2015;14:704–712. doi: 10.1158/1535-7163.MCT-14-0927-T. PubMed DOI

Ren M., Cowell J.K. Constitutive Notch pathway activation in murine ZMYM2-FGFR1-induced T-cell lymphomas associated with atypical myeloproliferative disease. Blood. 2011;117:6837–6847. doi: 10.1182/blood-2010-07-295725. PubMed DOI PMC

Agerstam H., Järås M., Andersson A., Johnels P., Hansen N., Lassen C., Rissler M., Gisselsson D., Olofsson T., Richter J., et al. Modeling the human 8p11-myeloproliferative syndrome in immunodeficient mice. Blood. 2010;116:2103–2111. doi: 10.1182/blood-2009-05-217182. PubMed DOI

Chase A., Grand F.H., Cross N.C.P.P. Activity of TKI258 against primary cells and cell lines with FGFR1 fusion genes associated with the 8p11 myeloproliferative syndrome. Blood. 2007;110:3729–3734. doi: 10.1182/blood-2007-02-074286. PubMed DOI

Peiris M.N., Meyer A.N., Nelson K.N., Bisom-Rapp E.W., Donoghue D.J. Oncogenic fusion protein BCR-FGFR1 requires the breakpoint cluster region-mediated oligomerization and chaperonin Hsp90 for activation. Haematologica. 2020;105:1262–1273. doi: 10.3324/haematol.2019.220871. PubMed DOI PMC

Oliveira D.M., Mirante T., Mignogna C., Scrima M., Migliozzi S., Rocco G., Franco R., Corcione F., Viglietto G., Malanga D., et al. Simultaneous identification of clinically relevant single nucleotide variants, copy number alterations and gene fusions in solid tumors by targeted next-generation sequencing. Oncotarget. 2018;9:22749–22768. doi: 10.18632/oncotarget.25229. PubMed DOI PMC

Di Stefano A.L., Fucci A., Frattini V., Labussiere M., Mokhtari K., Zoppoli P., Marie Y., Bruno A., Boisselier B., Giry M., et al. Detection, characterization, and inhibition of FGFR-TACC fusions in IDH wild-type glioma. Clin. Cancer Res. 2015;21:3307–3317. doi: 10.1158/1078-0432.CCR-14-2199. PubMed DOI PMC

Singh D., Chan J.M., Zoppoli P., Niola F., Sullivan R., Castano A., Liu E.M., Reichel J., Porrati P., Pellegatta S., et al. Transforming fusions of FGFR and TACC genes in human glioblastoma. Science. 2012;337:1231–1235. doi: 10.1126/science.1220834. PubMed DOI PMC

Costa R., Carneiro B.A., Taxter T., Tavora F.A., Kalyan A., Pai S.A., Chae Y.K., Giles F.J. FGFR3-TACC3 fusion in solid tumors: Mini review. Oncotarget. 2016;7:55924–55938. doi: 10.18632/oncotarget.10482. PubMed DOI PMC

Weinstein J.N., Akbani R., Broom B.M., Wang W., Verhaak R.G.W., McConkey D., Lerner S., Morgan M., Creighton C.J., Smith C., et al. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014;507:315–322. doi: 10.1038/nature12965. PubMed DOI PMC

Guo G., Sun X., Chen C., Wu S., Huang P., Li Z., Dean M., Huang Y., Jia W., Zhou Q., et al. Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation. Nat. Genet. 2013;45:1459–1463. doi: 10.1038/ng.2798. PubMed DOI PMC

Bao Z.S., Chen H.M., Yang M.Y., Zhang C.B., Yu K., Ye W.L., Hu B.Q., Yan W., Zhang W., Akers J., et al. RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas. Genome Res. 2014;24:1765–1773. doi: 10.1101/gr.165126.113. PubMed DOI PMC

Wang R., Wang L., Li Y., Hu H., Shen L., Shen X., Pan Y., Ye T., Zhang Y., Luo X., et al. FGFR1/3 tyrosine kinase fusions define a unique molecular subtype of non-small cell lung cancer. Clin. Cancer Res. 2014;20:4107–4114. doi: 10.1158/1078-0432.CCR-14-0284. PubMed DOI

Kim Y., Hammerman P.S., Kim J., Yoon J.A., Lee Y., Sun J.M., Wilkerson M.D., Pedamallu C.S., Cibulskis K., Yoo Y.K., et al. Integrative and comparative genomic analysis of lung squamous cell carcinomas in East Asian patients. J. Clin. Oncol. 2014;32:121–128. doi: 10.1200/JCO.2013.50.8556. PubMed DOI PMC

Javle M., Rashid A., Churi C., Kar S., Zuo M., Eterovic A.K., Nogueras-Gonzalez G.M., Janku F., Shroff R.T., Aloia T.A., et al. Molecular characterization of gallbladder cancer using somatic mutation profiling. Hum. Pathol. 2014;45:701–708. doi: 10.1016/j.humpath.2013.11.001. PubMed DOI PMC

Yuan L., Liu Z.H., Lin Z.R., Xu L.H., Zhong Q., Zeng M.S. Recurrent FGFR3-TACC3 fusion gene in nasopharyngeal carcinoma. Cancer Biol. Ther. 2014;15:1613–1621. doi: 10.4161/15384047.2014.961874. PubMed DOI PMC

Carneiro B.A., Elvin J.A., Kamath S.D., Ali S.M., Paintal A.S., Restrepo A., Berry E., Giles F.J., Johnson M.L. FGFR3-TACC3: A novel gene fusion in cervical cancer. Gynecol. Oncol. Rep. 2015;13:53–56. doi: 10.1016/j.gore.2015.06.005. PubMed DOI PMC

Lawrence M.S., Sougnez C., Lichtenstein L., Cibulskis K., Lander E., Gabriel S.B., Getz G., Ally A., Balasundaram M., Birol I., et al. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517:576–582. doi: 10.1038/nature14129. PubMed DOI PMC

Majewski I.J., Mittempergher L., Davidson N.M., Bosma A., Willems S.M., Horlings H.M., De Rink I., Greger L., Hooijer G.K.J., Peters D., et al. Identification of recurrent FGFR3 fusion genes in lung cancer through kinome-centred RNA sequencing. J. Pathol. 2013;230:270–276. doi: 10.1002/path.4209. PubMed DOI

Mizukami T., Sakai K., Naruki S., Taniyama T., Horie Y., Izawa N., Tsuda T., Fujino T., Boku N., Yasuda H., et al. Identification of a FGFR3-TACC3 fusion in esophageal cancer. Ann. Oncol. 2017;28:437–438. doi: 10.1093/annonc/mdw550. PubMed DOI

Capelletti M., Dodge M.E., Ercan D., Hammerman P.S., Park S.-I., Kim J., Sasaki H., Jablons D.M., Lipson D., Young L., et al. Identification of recurrent FGFR3-TACC3 fusion oncogenes from lung adenocarcinoma. Clin. Cancer Res. 2014;20:6551–6558. doi: 10.1158/1078-0432.CCR-14-1337. PubMed DOI

Nelson K.N., Meyer A.N., Siari A., Campos A.R., Motamedchaboki K., Donoghue D.J. Oncogenic gene fusion FGFR3-TACC3 Is regulated by tyrosine phosphorylation. Mol. Cancer Res. 2016;14:458–469. doi: 10.1158/1541-7786.MCR-15-0497. PubMed DOI

Nelson K.N., Meyer A.N., Wang C.G., Donoghue D.J. Oncogenic driver FGFR3-TACC3 is dependent on membrane trafficking and ERK signaling. Oncotarget. 2018;9:34306–34319. doi: 10.18632/oncotarget.26142. PubMed DOI PMC

Parker B.C., Annala M.J., Cogdell D.E., Granberg K.J., Sun Y., Ji P., Li X., Gumin J., Zheng H., Hu L., et al. The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma. J. Clin. Invest. 2013;123:855–865. doi: 10.1172/JCI67144. PubMed DOI PMC

Sievers P., Stichel D., Schrimpf D., Sahm F., Koelsche C., Reuss D.E., Wefers A.K., Reinhardt A., Huang K., Ebrahimi A., et al. FGFR1:TACC1 fusion is a frequent event in molecularly defined extraventricular neurocytoma. Acta Neuropathol. 2018;136:293–302. doi: 10.1007/s00401-018-1882-3. PubMed DOI

Bale T.A. FGFR- gene family alterations in low-grade neuroepithelial tumors. Acta Neuropathol. Commun. 2020;8:21. doi: 10.1186/s40478-020-00898-6. PubMed DOI PMC

Zhang J., Wu G., Miller C.P., Tatevossian R.G., Dalton J.D., Tang B., Orisme W., Punchihewa C., Parker M., Qaddoumi I., et al. Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Nat. Genet. 2013;45:602–612. doi: 10.1038/ng.2611. PubMed DOI PMC

Shi E., Chmielecki J., Tang C.M., Wang K., Heinrich M.C., Kang G., Corless C.L., Hong D., Fero K.E., Murphy J.D., et al. FGFR1 and NTRK3 actionable alterations in “Wild-Type” gastrointestinal stromal tumors. J. Transl. Med. 2016;14:1–11. doi: 10.1186/s12967-016-1075-6. PubMed DOI PMC

Lucas C.H.G., Gupta R., Doo P., Lee J.C., Cadwell C.R., Ramani B., Hofmann J.W., Sloan E.A., Kleinschmidt-Demasters B.K., Lee H.S., et al. Comprehensive analysis of diverse low-grade neuroepithelial tumors with FGFR1 alterations reveals a distinct molecular signature of rosette-forming glioneuronal tumor. Acta Neuropathol. Commun. 2020;8:1–17. doi: 10.1186/s40478-020-01027-z. PubMed DOI PMC

Sievers P., Schrimpf D., Stichel D., Reuss D.E., Hasselblatt M., Hagel C., Staszewski O., Hench J., Frank S., Brandner S., et al. Posterior fossa pilocytic astrocytomas with oligodendroglial features show frequent FGFR1 activation via fusion or mutation. Acta Neuropathol. 2020;139:403–406. doi: 10.1007/s00401-019-02097-7. PubMed DOI

Daoud E.V., Patel A., Gagan J., Raisanen J.M., Snipes G.J., Mantilla E., Krothapally R., Hatanpaa K.J., Pan E. Spinal Cord Pilocytic Astrocytoma With FGFR1-TACC1 Fusion and Anaplastic Transformation. J. Neuropathol. Exp. Neurol. 2021;80:283–285. doi: 10.1093/jnen/nlaa122. PubMed DOI

Devereaux K.A., Weiel J.J., Mills A.M., Kunder C.A., Longacre T.A. Neurofibrosarcoma Revisited: An Institutional Case Series of Uterine Sarcomas Harboring Kinase-related Fusions With Report of a Novel FGFR1-TACC1 Fusion. Am. J. Surg. Pathol. 2021;45:638–652. doi: 10.1097/PAS.0000000000001644. PubMed DOI

Borad M.J., Champion M.D., Egan J.B., Liang W.S., Fonseca R., Bryce A.H., McCullough A.E., Barrett M.T., Hunt K., Patel M.D., et al. Integrated Genomic Characterization Reveals Novel, Therapeutically Relevant Drug Targets in FGFR and EGFR Pathways in Sporadic Intrahepatic Cholangiocarcinoma. PLoS Genet. 2014;10:e1004135. doi: 10.1371/journal.pgen.1004135. PubMed DOI PMC

Ying X., Tu J., Wang W., Li X., Xu C., Ji J. FGFR2-BICC1: A subtype of FGFR2 oncogenic fusion variant in cholangiocarcinoma and the response to sorafenib. Onco. Targets. Ther. 2019;12:9303–9307. doi: 10.2147/OTT.S218796. PubMed DOI PMC

Ross J.S., Wang K., Gay L., Al-Rohil R., Rand J.V., Jones D.M., Lee H.J., Sheehan C.E., Otto G.A., Palmer G., et al. New Routes to Targeted Therapy of Intrahepatic Cholangiocarcinomas Revealed by Next-Generation Sequencing. Oncologist. 2014;19:235–242. doi: 10.1634/theoncologist.2013-0352. PubMed DOI PMC

Mazzaferro V., El-Rayes B.F., Droz dit Busset M., Cotsoglou C., Harris W.P., Damjanov N., Masi G., Rimassa L., Personeni N., Braiteh F., et al. Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma. Br. J. Cancer. 2019;120:165–171. doi: 10.1038/s41416-018-0334-0. PubMed DOI PMC

Scheiter A., Keil F., Lüke F., Grosse J., Verloh N., Opitz S., Schlosser S., Kandulski A., Pukrop T., Dietmaier W., et al. Identification and In-Depth Analysis of the Novel FGFR2-NDC80 Fusion in a Cholangiocarcinoma Patient: Implication for Therapy. Curr. Oncol. 2021;28:112. doi: 10.3390/curroncol28020112. PubMed DOI PMC

Seo J.S., Ju Y.S., Lee W.C., Shin J.Y., Lee J.K., Bleazard T., Lee J., Jung Y.J., Kim J.O., Shin J.Y., et al. The transcriptional landscape and mutational profile of lung adenocarcinoma. Genome Res. 2012;22:2109–2119. doi: 10.1101/gr.145144.112. PubMed DOI PMC

Qin A., Johnson A., Ross J.S., Miller V.A., Ali S.M., Schrock A.B., Gadgeel S.M. Detection of Known and Novel FGFR Fusions in Non–Small Cell Lung Cancer by Comprehensive Genomic Profiling. J. Thorac. Oncol. 2019;14:54–62. doi: 10.1016/j.jtho.2018.09.014. PubMed DOI

Tabernero J., Bahleda R., Dienstmann R., Infante J.R., Mita A., Italiano A., Calvo E., Moreno V., Adamo B., Gazzah A., et al. Phase I dose-escalation study of JNJ-42756493, an oral pan-fibroblast growth factor receptor inhibitor, in patients with advanced solid tumors. J. Clin. Oncol. 2015;33:3401–3408. doi: 10.1200/JCO.2014.60.7341. PubMed DOI

Popovici C., Zhang B., Grégoire M.J., Jonveaux P., Lafage-Pochitaloff M., Birnbaum D., Pébusque M.J. The t(6;8)(q27;p11) translocation in a stem cell myeloproliferative disorder fuses a novel gene, FOP, to Fibroblast Growth Factor Receptor 1. Blood. 1999;93:1381–1389. doi: 10.1182/blood.V93.4.1381. PubMed DOI

Sohal J., Chase A., Mould S., Corcoran M., Oscier D., Iqbal S., Parker S., Welborn J., Harris R.I., Martinelli G., et al. Identification of four new translocations involvingFGFR1 in myeloid disorders. Genes, Chromosom. Cancer. 2001;32:155–163. doi: 10.1002/gcc.1177. PubMed DOI

Vannier J.P., Bizet M., Bastard C., Bernard A., Ducastelle T., Tron P. Simultaneous occurrence of a T-cell lymphoma and a chronic myelogenous leukemia with an unusual karyotype. Leuk. Res. 1984;8:647–657. doi: 10.1016/0145-2126(84)90013-4. PubMed DOI

Vizmanos J.L., Hernández R., Vidal M.J., Larráyoz M.J., Odero M.D., Marín J., Ardanaz M.T., Calasanz M.J., Cross N.C.P. Clinical variability of patients with the t(6;8)(q27;p12) and FGFR1OP-FGFR1 fusion: Two further cases. Hematol. J. 2004;5:534–537. doi: 10.1038/sj.thj.6200561. PubMed DOI

Chaffanet M., Popovici C., Leroux D., Jacrot M., Adélaïde J., Dastugue N., Grégoire M.J., Hagemeijer A., Lafage-Pochitaloff M., Birnbaum D., et al. t(6;8), t(8;9) and t(8;13) translocations associated with stem cell myeloproliferative disorders have close or identical breakpoints in chromosome region 8p11-12. Oncogene. 1998;16:945–949. doi: 10.1038/sj.onc.1201601. PubMed DOI

Onozawa M., Ohmura K., Ibata M., Iwasaki J., Okada K., Kasahara I., Yamaguchi K., Kubota K., Fujisawa S., Shigematsu A., et al. The 8p11 myeloproliferative syndrome owing to rare FGFR1OP2-FGFR1 fusion. Eur. J. Haematol. 2011;86:347–349. doi: 10.1111/j.1600-0609.2010.01568.x. PubMed DOI

Macdonald D., Aguiar R.C., Mason P.J., Goldman J.M., Cross N.C. A new myeloproliferative disorder associated with chromosomal translocations involving 8p11: A review. Leukemia. 1995;9:1628–1630. PubMed

Macdonald D., Reiter A., Cross N.C.P. The 8p11 myeloproliferative syndrome: A distinct clinical entity caused by constitutive activation of FGFR1. Acta Haematol. 2002;107:101–107. doi: 10.1159/000046639. PubMed DOI

Friedhoff F., Rajendra B., Moody R., Alapatt T. Novel reciprocal translocation between chromosomes 8 and 9 found in a patient with myeloproliferative disorder. Cancer Genet. Cytogenet. 1983;9:391–394. doi: 10.1016/0165-4608(83)90088-2. PubMed DOI

Yamamoto K., Kawano H., Nishikawa S., Yakushijin K., Okamura A., Matsui T. A biphenotypic transformation of 8p11 myeloproliferative syndrome with CEP1/FGFR1 fusion gene. Eur. J. Haematol. 2006;77:349–354. doi: 10.1111/j.1600-0609.2006.00723.x. PubMed DOI

Park T.S., Song J., Kim J.S., Yang W.I., Song S., Kim S.J., Suh B., Choi J.R. 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;181:93–99. doi: 10.1016/j.cancergencyto.2007.11.011. PubMed DOI

Mozziconacci M.J., Carbuccia N., Prebet T., Charbonnier A., Murati A., Vey N., Chaffanet M., Birnbaum D. Common features of myeloproliferative disorders with t(8;9)(p12;q33) and CEP110-FGFR1 fusion: Report of a new case and review of the literature. Leuk. Res. 2008;32:1304–1308. doi: 10.1016/j.leukres.2007.11.012. PubMed DOI

Zhou L., Fu W., Yuan Z., Hou J. Complete molecular remission after interferon alpha treatment in a case of 8p11 myeloproliferative syndrome. Leuk. Res. 2010;34:e306–e307. doi: 10.1016/j.leukres.2010.06.027. PubMed DOI

Hu S., He Y., Zhu X., Li J., He H. Myeloproliferative disorders with t(8;9)(p12;q33): A case report and review of the literature. Pediatr. Hematol. Oncol. 2011;28:140–146. doi: 10.3109/08880018.2010.528170. PubMed DOI

Yamamoto S., Ebihara Y., Mochizuki S., Kawakita T., Kato S., Ooi J., Takahashi S., Tojo A., Yusa N., Furukawa Y., et al. Quantitative polymerase chain reaction detection of CEP110-FGFR1 fusion gene in a patient with 8p11 myeloproliferative syndrome. Leuk. Lymphoma. 2013;54:2068–2069. doi: 10.3109/10428194.2013.767455. PubMed DOI

Sarah O.-O., Anthony A., Titilope A., Alani S. The 8p12 myeloproliferative syndrome. Niger. Med. J. 2014;55:176. doi: 10.4103/0300-1652.129669. PubMed DOI PMC

Wehrli M., Oppliger Leibundgut E., Gattiker H.H., Manz M.G., Müller A.M.S., Goede J.S. Response to Tyrosine Kinase Inhibitors in Myeloproliferative Neoplasia with 8p11 Translocation and CEP110-FGFR1 Rearrangement. Oncologist. 2017;22:480–483. doi: 10.1634/theoncologist.2016-0354. PubMed DOI PMC

Sarthy J.F., Reddivalla N., Radhi M., Chastain K. Pediatric 8p11 eosinophilic myeloproliferative syndrome (EMS): A case report and review of the literature. Pediatr. Blood Cancer. 2017;64:1–8. doi: 10.1002/pbc.26310. PubMed DOI

Chen M., Wang K., Cai X., Zhang X., Chao H., Chen S., Shen H., Wang Q., Zhang R. Myeloid/lymphoid neoplasm with CEP110-FGFR1 fusion: An analysis of 16 cases show common features and poor prognosis. Hematology. 2021;26:153–159. doi: 10.1080/16078454.2020.1854493. PubMed DOI

Oscier D.G., Mufti G.J., Gardiner A., Hamblin T.J. Reciprocal translocation between chromosomes 8 and 9 in atypical chronic myeloid leukaemia. J. Med. Genet. 1985;22:398–401. doi: 10.1136/jmg.22.5.398. PubMed DOI PMC

Yamamoto S., Otsu M., Matsuzaka E., Konishi C., Takagi H., Hanada S., Mochizuki S., Nakauchi H., Imai K., Tsuji K., et al. Screening of drugs to treat 8p11 myeloproliferative syndrome using patient-derived induced pluripotent stem cells with fusion gene CEP110-FGFR1. PLoS ONE. 2015;10:e0120841. doi: 10.1371/journal.pone.0120841. PubMed DOI PMC

Brown L.M., Bartolo R.C., Davidson N.M., Schmidt B., Brooks I., Challis J., Petrovic V., Khuong-Quang D.A., Mechinaud F., Khaw S.L., et al. Targeted therapy and disease monitoring in CNTRL-FGFR1-driven leukaemia. Pediatr. Blood Cancer. 2019;66:1–5. doi: 10.1002/pbc.27897. PubMed DOI

Lewis J.P., Welborn J.L., Meyers F.J., Levy N.B., Roschak T. Mast cell disease followed by leukemia with clonal evolution. Leuk. Res. 1987;11:769–773. doi: 10.1016/0145-2126(87)90060-9. PubMed DOI

Jotterand Bellomo M., Mühlematter D., Wicht M., Delacrétaz F., Schmidt P.M. t(8;9)(p11;q32) in atypical chronic myeloid leukaemia: A new cytogenetic-clinicopathologic association? Br. J. Haematol. 1992;81:307–308. doi: 10.1111/j.1365-2141.1992.tb08225.x. PubMed DOI

Van den Berg H., Kroes W., van der Schoot C.E., Dee R., Pals S.T., Bouts T.H., Slater R.M. A young child with acquired t(8;9)(p11;q34): Additional proof that 8p11 is involved in mixed myeloid/T lymphoid malignancies. Leukemia. 1996;10:1252–1253. PubMed

Nakayama H., Inamitsu T., Ohga S., Kai T., Suda M., Matsuzaki A., Ueda K. Chronic myelomonocytic leukaemia with t(8;9)(p11;q34) in childhood: An example of the 8p11 myeloproliferative disorder? Br. J. Haematol. 1996;92:692–695. doi: 10.1046/j.1365-2141.1996.00386.x. PubMed DOI

Vandergoten P., Janssen M., Madoe V., Vanstraelen D. A myeloproliferative disorder with eosinophilia, a translocation t(8; 9)(p22;23) and a cerebellar degeneration in regression with interferon alpha therapy. Acta Haematol. 1998;100:8.

Guasch G., Mack G.J., Popovici C., Dastugue N., Birnbaum D., Rattner J.B., Pébusque M.J. FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33) Blood. 2000;95:1788–1796. doi: 10.1182/blood.V95.5.1788.005k15_1788_1796. PubMed DOI

Heiss S., Erdel M., Gunsilius E., Nachbaur D., Tzankov A. Myelodysplastic/myeloproliferative disease with erythropoietic hyperplasia (erythroid preleukemia) and the unique translocation (8;9)(p23;p24): First description of a case. Hum. Pathol. 2005;36:1148–1151. doi: 10.1016/j.humpath.2005.07.020. PubMed DOI

Chen J., Williams I.R., Lee B.H., Duclos N., Huntly B.J.P., Donoghue D.J., Gilliland D.G. Constitutively activated FGFR3 mutants signal through PLCγ-dependent and -independent pathways for hematopoietic transformation. Blood. 2005;106:328–337. doi: 10.1182/blood-2004-09-3686. PubMed DOI PMC

Yamaguchi T., Kakefuda R., Tajima N., Sowa Y., Sakai T. Antitumor activities of JTP-74057 (GSK1120212), a novel MEK1/2 inhibitor, on colorectal cancer cell lines in vitro and in vivo. Int. J. Oncol. 2011;39:23–31. doi: 10.3892/ijo.2011.1015. PubMed DOI

Guagnano V., Furet P., Spanka C., Bordas V., Le Douget M., Stamm C., Brueggen J., Jensen M.R., Schnell C., Schmid H., 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;54:7066–7083. doi: 10.1021/jm2006222. PubMed DOI

Liu P.C.C., Koblish H., Wu L., Bowman K., Diamond S., DiMatteo D., Zhang Y., Hansbury M., Rupar M., Wen X., et al. INCB054828 (pemigatinib), a potent and selective inhibitor of fibroblast growth factor receptors 1, 2, and 3, displays activity against genetically defined tumor models. PLoS ONE. 2020;15:e231877. doi: 10.1371/journal.pone.0231877. PubMed DOI PMC

Hood F.E., Williams S.J., Burgess S.G., Richards M.W., Roth D., Straube A., Pfuhl M., Bayliss R., Royle S.J. Coordination of adjacent domains mediates TACC3-ch-TOG-clathrin assembly and mitotic spindle binding. J. Cell Biol. 2013;202:463–478. doi: 10.1083/jcb.201211127. PubMed DOI PMC

Hood F.E., Royle S.J. Pulling it together: The mitotic function of TACC3. Bioarchitecture. 2011;1:105–109. doi: 10.4161/bioa.1.3.16518. PubMed DOI PMC

Nixon F.M., Gutiérrez-Caballero C., Hood F.E., Booth D.G., Prior I.A., Royle S.J. The mesh is a network of microtubule connectors that stabilizes individual kinetochore fibers of the mitotic spindle. Elife. 2015;4:1–21. doi: 10.7554/eLife.07635. PubMed DOI PMC

Sarkar S., Ryan E.L., Royle S.J. FGFR3-TACC3 cancer gene fusions cause mitotic defects by removal of endogenous TACC3 from the mitotic spindle. Open Biol. 2017;7 doi: 10.1098/rsob.170080. PubMed DOI PMC

Yao R., Natsume Y., Saiki Y., Shioya H., Takeuchi K., Yamori T., Toki H., Aoki I., Saga T., Noda T. Disruption of Tacc3 function leads to in vivo tumor regression. Oncogene. 2012;31:135–148. doi: 10.1038/onc.2011.235. PubMed DOI

Yao R., Oyanagi J., Natsume Y., Kusama D., Kato Y., Nagayama S., Noda T. Suppression of intestinal tumors by targeting the mitotic spindle of intestinal stem cells. Oncogene. 2016;35:6109–6119. doi: 10.1038/onc.2016.148. PubMed DOI

Akbulut O., Lengerli D., Saatci O., Duman E., Seker U.O.S., Isik A., Akyol A., Caliskan B., Banoglu E., Sahin O. A highly potent TACC3 inhibitor as a novel anticancer drug candidate. Mol. Cancer Ther. 2020;19:1243–1254. doi: 10.1158/1535-7163.MCT-19-0957. PubMed DOI

Kinoshita K., Noetzel T.L., Pelletier L., Mechtler K., Drechsel D.N., Schwager A., Lee M., Raff J.W., Hyman A.A. Aurora A phosphorylation of TACC3/maskin is required for centrosome-dependent microtubule assembly in mitosis. J. Cell Biol. 2005;170:1047–1055. doi: 10.1083/jcb.200503023. PubMed DOI PMC

Adams M., Simms R.J., Abdelhamed Z., Dawe H.R., Szymanska K., Logan C.V., Wheway G., Pitt E., Gull K., Knowles M.A., et al. A meckelin-filamin a interaction mediates ciliogenesis. Hum. Mol. Genet. 2012;21:1272–1286. doi: 10.1093/hmg/ddr557. PubMed DOI PMC

Qie Y., Wang L., Du E., Chen S., Lu C., Ding N., Yang K., Xu Y. TACC3 promotes prostate cancer cell proliferation and restrains primary cilium formation. Exp. Cell Res. 2020;390 doi: 10.1016/j.yexcr.2020.111952. PubMed DOI

Still I.H., Hamilton M., Vince P., Wolfman A., Cowell J.K. Cloning of TACC1, an embryonically expressed, potentially transforming coiled coil containing gene, from the 8p11 breast cancer amplicon. Oncogene. 1999;18:4032–4038. doi: 10.1038/sj.onc.1202801. PubMed DOI

Peset I., Vernos I. The TACC proteins: TACC-ling microtubule dynamics and centrosome function. Trends Cell Biol. 2008;18:379–388. doi: 10.1016/j.tcb.2008.06.005. PubMed DOI

Gergely F., Karlsson C., Still I., Cowell J., Kilmartin J., Raff J.W. The TACC domain identifies a family of centrosomal proteins that can interact with microtubules. Proc. Natl. Acad. Sci. USA. 2000;97:14352–14357. doi: 10.1073/pnas.97.26.14352. PubMed DOI PMC

Conte N., Delaval B., Ginestier C., Ferrand A., Isnardon D., Larroque C., Prigent C., Séraphin B., Jacquemier J., Birnbaum D. TACC1-chTOG-Aurora A protein complex in breast cancer. Oncogene. 2003;22:8102–8116. doi: 10.1038/sj.onc.1206972. PubMed DOI

Cristinziano G., Porru M., Lamberti D., Buglioni S., Rollo F., Amoreo C.A., Manni I., Giannarelli D., Cristofoletti C., Russo G., et al. FGFR2 fusion proteins drive oncogenic transformation of mouse liver organoids towards cholangiocarcinoma. J. Hepatol. 2021;11:3–5. doi: 10.1016/j.jhep.2021.02.032. PubMed DOI

Parker B.C., Engels M., Annala M., Zhang W. Emergence of FGFR family gene fusions as therapeutic targets in a wide spectrum of solid tumours. J. Pathol. 2014;232:4–15. doi: 10.1002/path.4297. PubMed DOI

Bahleda R., Meric-Bernstam F., Goyal L., Tran B., He Y., Yamamiya I., Benhadji K.A., Matos I., Arkenau H.-T. Phase I, first-in-human study of futibatinib, a highly selective, irreversible FGFR1–4 inhibitor in patients with advanced solid tumors. Ann. Oncol. 2020;31:1405–1412. doi: 10.1016/j.annonc.2020.06.018. PubMed DOI PMC

Goyal L., Saha S.K., Liu L.Y., Siravegna G., Leshchiner I., Ahronian L.G., Lennerz J.K., Vu P., Deshpande V., Kambadakone A., et al. Polyclonal Secondary FGFR2 Mutations Drive Acquired Resistance to FGFR Inhibition in Patients with FGFR2 Fusion–Positive Cholangiocarcinoma. Cancer Discov. 2017;7:252–263. doi: 10.1158/2159-8290.CD-16-1000. PubMed DOI PMC

Mahone M., Saffman E.E., Lasko P.F. Localized Bicaudal-C RNA encodes a protein containing a KH domain, the RNA binding motif of FMR1. EMBO J. 1995;14:2043–2055. doi: 10.1002/j.1460-2075.1995.tb07196.x. PubMed DOI PMC

Park S., Blaser S., Marchal M.A., Houston D.W., Sheets M.D. A gradient of maternal Bicaudal-C controls vertebrate embryogenesis via translational repression of mRNAs encoding cell fate regulators. Development. 2016;143:864–871. doi: 10.1242/dev.131359. PubMed DOI PMC

Wessely O., De Robertis E.M. The Xenopus homologue of Bicaudal-C is a localized maternal mRNA that can induce endoderm formation. Development. 2000;127:2053–2062. doi: 10.1242/dev.127.10.2053. PubMed DOI PMC

Dowdle M.E., Park S., Blaser Imboden S., Fox C.A., Houston D.W., Sheets M.D. A single KH domain in Bicaudal-C links mRNA binding and translational repression functions to maternal development. Development. 2019;146 doi: 10.1242/dev.172486. PubMed DOI PMC

Saffman E.E., Styhler S., Rother K., Li W., Richard S., Lasko P. Premature translation of oskar in oocytes lacking the RNA-binding protein bicaudal-C. Mol. Cell. Biol. 1998;18:4855–4862. doi: 10.1128/MCB.18.8.4855. PubMed DOI PMC

Tran U., Zakin L., Schweickert A., Agrawal R., Döger R., Blum M., De Robertis E.M., Wessely O. The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity. Development. 2010;137:1107–1116. doi: 10.1242/dev.046045. PubMed DOI PMC

Cogswell C., Price S.J., Hou X., Guay-Woodford L.M., Flaherty L., Bryda E.C. Positional cloning of jcpk/bpk locus of the mouse. Mamm. Genome. 2003;14:242–249. doi: 10.1007/s00335-002-2241-0. PubMed DOI

Lemaire L.A., Goulley J., Kim Y.H., Carat S., Jacquemin P., Rougemont J., Constam D.B., Grapin-Botton A. Bicaudal C1 promotes pancreatic NEUROG3+ endocrine progenitor differentiation and ductal morphogenesis. Development. 2015;142:858–870. doi: 10.1242/dev.114611. PubMed DOI

Maisonneuve C., Guilleret I., Vick P., Weber T., Andre P., Beyer T., Blum M., Constam D.B. Bicaudal C, a novel regulator of Dvl signaling abutting RNA-processing bodies, controls cilia orientation and leftward flow. Development. 2009;136:3019–3030. doi: 10.1242/dev.038174. PubMed DOI

Guay-Woodford L.M., Bryda E.C., Christine B., Lindsey J.R., Collier W.R., Avner E.D., D’Eustachio P., Flaherty L. Evidence that two phenotypically distinct mouse PKD mutations, bpk and jcpk, are allelic. Kidney Int. 1996;50:1158–1165. doi: 10.1038/ki.1996.423. PubMed DOI

Flaherty L., Bryda E.C., Collins D., Rudofsky U., Montogomery J.C. New mouse model for polycystic kidney disease with both recessive and dominant gene effects. Kidney Int. 1995;47:552–558. doi: 10.1038/ki.1995.69. PubMed DOI

Bouvrette D.J., Sittaramane V., Heidel J.R., Chandrasekhar A., Bryda E.C. Knockdown of bicaudal C in zebrafish (Danio rerio) causes cystic kidneys: A nonmammalian model of polycystic kidney disease. Comp. Med. 2010;60:96–106. PubMed PMC

Gamberi C., Hipfner D.R., Trudel M., Lubell W.D. Bicaudal C mutation causes myc and TOR pathway up-regulation and polycystic kidney disease-like phenotypes in Drosophila. PLoS Genet. 2017;13:e1006694. doi: 10.1371/journal.pgen.1006694. PubMed DOI PMC

Iaconis D., Monti M., Renda M., Van Koppen A., Tammaro R., Chiaravalli M., Cozzolino F., Pignata P., Crina C., Pucci P., et al. The centrosomal OFD1 protein interacts with the translation machinery and regulates the synthesis of specific targets. Sci. Rep. 2017;7:1224. doi: 10.1038/s41598-017-01156-x. PubMed DOI PMC

Rothé B., Gagnieux C., Leal-Esteban L.C., Constam D.B. Role of the RNA-binding protein Bicaudal-C1 and interacting factors in cystic kidney diseases. Cell. Signal. 2020;68:109499. doi: 10.1016/j.cellsig.2019.109499. PubMed DOI

Kraus M.R.C., Clauin S., Pfister Y., Di Maïo M., Ulinski T., Constam D., Bellanné-Chantelot C., Grapin-Botton A. Two mutations in human BICC1 resulting in wnt pathway hyperactivity associated with cystic renal dysplasia. Hum. Mutat. 2012;33:86–90. doi: 10.1002/humu.21610. PubMed DOI

Mesner L.D., Ray B., Hsu Y.H., Manichaikul A., Lum E., Bryda E.C., Rich S.S., Rosen C.J., Criqui M.H., Allison M., et al. Bicc1 is a genetic determinant of osteoblastogenesis and bone mineral density. J. Clin. Invest. 2014;124:2736–2749. doi: 10.1172/JCI73072. PubMed DOI PMC

Rothé B., Leal-Esteban L., Bernet F., Urfer S., Doerr N., Weimbs T., Iwaszkiewicz J., Constam D.B. Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA. Mol. Cell. Biol. 2015;35:3339–3353. doi: 10.1128/MCB.00341-15. PubMed DOI PMC

Bouvrette D.J., Price S.J., Bryda E.C. K homology domains of the mouse polycystic kidney disease-related protein, Bicaudal-C (Bicc1), mediate RNA binding in vitro. Nephron. Exp. Nephrol. 2008;108:e27–e34. doi: 10.1159/000112913. PubMed DOI

Wimbish R.T., DeLuca J.G. Hec1/Ndc80 Tail Domain Function at the Kinetochore-Microtubule Interface. Front. Cell Dev. Biol. 2020;8:1–16. doi: 10.3389/fcell.2020.00043. PubMed DOI PMC

Qu Y., Li J., Cai Q., Liu B. Hec1/Ndc80 is overexpressed in human gastric cancer and regulates cell growth. J. Gastroenterol. 2014;49:408–418. doi: 10.1007/s00535-013-0809-y. PubMed DOI

Wang G., Jiang Q., Zhang C. The role of mitotic kinases in coupling the centrosome cycle with the assembly of the mitotic spindle. J. Cell Sci. 2014;127:4111–4122. doi: 10.1242/jcs.151753. PubMed DOI

Bièche I., Vacher S., Lallemand F., Tozlu-Kara S., Bennani H., Beuzelin M., Driouch K., Rouleau E., Lerebours F., Ripoche H., et al. Expression analysis of mitotic spindle checkpoint genes in breast carcinoma: Role of NDC80/HEC1 in early breast tumorigenicity, and a two-gene signature for aneuploidy. Mol. Cancer. 2011;10:1–18. doi: 10.1186/1476-4598-10-23. PubMed DOI PMC

Hu C.M., Zhu J., Guo X.E., Chen W., Qiu X.L., Ngo B., Chien R., Wang Y.V., Tsai C.Y., Wu G., et al. Novel small molecules disrupting Hec1/Nek2 interaction ablate tumor progression by triggering Nek2 degradation through a death-trap mechanism. Oncogene. 2015;34:1220–1230. doi: 10.1038/onc.2014.67. PubMed DOI PMC

Diaz-Rodríguez E., Sotillo R., Schvartzman J.M., Benezra R. Hec1 overexpression hyperactivates the mitotic checkpoint and induces tumor formation in vivo. Proc. Natl. Acad. Sci. USA. 2008;105:16719–16724. doi: 10.1073/pnas.0803504105. PubMed DOI PMC

Leber B., Maier B., Fuchs F., Chi J., Riffel P., Anderhub S., Wagner L., Ho A.D., Salisbury J.L., Boutros M., et al. Proteins required for centrosome clustering in cancer cells. Sci. Transl. Med. 2010;2 doi: 10.1126/scitranslmed.3000915. PubMed DOI

Wu G., Qiu X.L., Zhou L., Zhu J., Chamberlin R., Lau J., Chen P.L., Lee W.H. Small molecule targeting the Hec1/Nek2 mitotic pathway suppresses tumor cell growth in culture and in animal. Cancer Res. 2008;68:8393–8399. doi: 10.1158/0008-5472.CAN-08-1915. PubMed DOI PMC

Huang L.Y.L., Chang C.C., Lee Y.S., Huang J.J., Chuang S.H., Chang J.M., Kao K.J., Lau G.M.G., Tsai P.Y., Liu C.W., et al. Inhibition of Hec1 as a novel approach for treatment of primary liver cancer. Cancer Chemother. Pharmacol. 2014;74:511–520. doi: 10.1007/s00280-014-2540-7. PubMed DOI

Hall T.G., Yu Y., Eathiraj S., Wang Y., Savage R.E., Lapierre J.-M., Schwartz B., Abbadessa G. Preclinical Activity of ARQ 087, a Novel Inhibitor Targeting FGFR Dysregulation. PLoS ONE. 2016;11:e0162594. doi: 10.1371/journal.pone.0162594. PubMed DOI PMC

Gai M., Bianchi F.T., Vagnoni C., Vernì F., Bonaccorsi S., Pasquero S., Berto G.E., Sgrò F., Chiotto A.A., Annaratone L., et al. ASPM and CITK regulate spindle orientation by affecting the dynamics of astral microtubules. EMBO Rep. 2017;18:1870. doi: 10.15252/embr.201745023. PubMed DOI PMC

Watanabe S., De Zan T., Ishizaki T., Narumiya S. Citron kinase mediates transition from constriction to abscission through its coiled-coil domain. J. Cell Sci. 2013;126:1773–1784. doi: 10.1242/jcs.116608. PubMed DOI

Bassi Z.I., Audusseau M., Riparbelli M.G., Callaini G., D’Avino P.P. Citron kinase controls a molecular network required for midbody formation in cytokinesis. Proc. Natl. Acad. Sci. USA. 2013;110:9782–9787. doi: 10.1073/pnas.1301328110. PubMed DOI PMC

Gruneberg U., Neef R., Li X., Chan E.H.Y., Chalamalasetty R.B., Nigg E.A., Barr F.A. KIF14 and citron kinase act together to promote efficient cytokinesis. J. Cell Biol. 2006;172:363–372. doi: 10.1083/jcb.200511061. PubMed DOI PMC

Wu Z., Zhu X., Xu W., Zhang Y., Chen L., Qiu F., Zhang B., Wu L., Peng Z., Tang H. Up-regulation of CIT promotes the growth of colon cancer cells. Oncotarget. 2017;8:71954–71964. doi: 10.18632/oncotarget.18615. PubMed DOI PMC

Fu Y., Huang J., Wang K.S., Zhang X., Han Z.G. RNA interference targeting CITRON can significantly inhibit the proliferation of hepatocellular carcinoma cells. Mol. Biol. Rep. 2011;38:693–702. doi: 10.1007/s11033-010-0156-5. PubMed DOI

Ehrlichova M., Mohelnikova-Duchonova B., Hrdy J., Brynychova V., Mrhalova M., Kodet R., Rob L., Pluta M., Gut I., Soucek P., et al. The association of taxane resistance genes with the clinical course of ovarian carcinoma. Genomics. 2013;102:96–101. doi: 10.1016/j.ygeno.2013.03.005. PubMed DOI

Meng D., Yu Q., Feng L., Luo M., Shao S., Huang S., Wang G., Jing X., Tong Z., Zhao X., et al. Citron kinase (CIT-K) promotes aggressiveness and tumorigenesis of breast cancer cells in vitro and in vivo: Preliminary study of the underlying mechanism. Clin. Transl. Oncol. 2019;21:910–923. doi: 10.1007/s12094-018-02003-9. PubMed DOI

Liu Z., Yan H., Yang Y., Wei L., Xia S., Xiu Y. Down-regulation of CIT can inhibit the growth of human bladder cancer cells. Biomed. Pharmacother. 2020;124:109830. doi: 10.1016/j.biopha.2020.109830. PubMed DOI

Liu J., Dou J., Wang W., Liu H., Qin Y., Yang Q., Jiang W., Liang Y., Liu Y., He J., et al. High expression of citron kinase predicts poor prognosis of prostate cancer. Oncol. Lett. 2020;19:1815–1823. doi: 10.3892/ol.2020.11254. PubMed DOI PMC

Pallavicini G., Iegiani G., Berto G.E., Calamia E., Trevisiol E., Veltri A., Allis S., Di Cunto F. CITK loss inhibits growth of group 3 and group 4 medulloblastoma cells and sensitizes them to DNA-damaging agents. Cancers. 2020;12:542. doi: 10.3390/cancers12030542. PubMed DOI PMC

Di Cunto F., Imarisio S., Hirsch E., Broccoli V., Bulfone A., Migheli A., Atzori C., Turco E., Triolo R., Dotto G.P., et al. Defective neurogenesis in citron kinase knockout mice by altered cytokinesis and massive apoptosis. Neuron. 2000;28:115–127. doi: 10.1016/S0896-6273(00)00090-8. PubMed DOI

Di Cunto F., Imarisio S., Camera P., Boitani C., Altruda F., Silengo L. Essential role of citron kinase in cytokinesis of spermatogenic precursors. J. Cell Sci. 2002;115:4819–4826. doi: 10.1242/jcs.00163. PubMed DOI

Mick D.U., Rodrigues R.B., Leib R.D., Adams C.M., Chien A.S., Gygi S.P., Nachury M. V Proteomics of Primary Cilia by Proximity Labeling. Dev. Cell. 2015;35:497–512. doi: 10.1016/j.devcel.2015.10.015. PubMed DOI PMC

Kuhns S., Schmidt K.N., Reymann J., Gilbert D.F., Neuner A., Hub B., Carvalho R., Wiedemann P., Zentgraf H., Erfle H., et al. The microtubule affinity regulating kinase MARK4 promotes axoneme extension during early ciliogenesis. J. Cell Biol. 2013;200:505–522. doi: 10.1083/jcb.201206013. PubMed DOI PMC

Anastas S.B., Mueller D., Semple-Rowland S.L., Breunig J.J., Sarkisian M.R. Failed cytokinesis of neural progenitors in citron kinase-deficient rats leads to multiciliated neurons. Cereb. Cortex. 2011;21:338–344. doi: 10.1093/cercor/bhq099. PubMed DOI

Karkera J.D., Cardona G.M., Bell K., Gaffney D., Portale J.C., Santiago-Walker A., Moy C.H., King P., Sharp M., Bahleda R., et al. Oncogenic characterization and pharmacologic sensitivity of activating Fibroblast Growth Factor Receptor (FGFR) genetic alterations to the selective FGFR inhibitor erdafitinib. Mol. Cancer Ther. 2017;16:1717–1726. doi: 10.1158/1535-7163.MCT-16-0518. PubMed DOI

Romio L., Fry A.M., Winyard P.J.D., Malcolm S., Woolf A.S., Feather S.A. OFD1 is a centrosomal/basal body protein expressed during mesenchymal-epithelial transition in human nephrogenesis. J. Am. Soc. Nephrol. 2004;15:2556–2568. doi: 10.1097/01.ASN.0000140220.46477.5C. PubMed DOI

Ferrante M.I., Zullo A., Barra A., Bimonte S., Messaddeq N., Studer M., Dollé P., Franco B. Oral-facial-digital type I protein is required for primary cilia formation and left-right axis specification. Nat. Genet. 2006;38:112–117. doi: 10.1038/ng1684. PubMed DOI

Singla V., Romaguera-Ros M., Garcia-Verdugo J.M., Reiter J.F. Ofd1, a Human Disease Gene, Regulates the Length and Distal Structure of Centrioles. Dev. Cell. 2010;18:410–424. doi: 10.1016/j.devcel.2009.12.022. PubMed DOI PMC

Lopes C.A.M., Prosser S.L., Romio L., Hirst R.A., O’Callaghan C., Woolf A.S., Fry A.M. Centriolar satellites are assembly points for proteins implicated in human ciliopathies, including oral-facial-digital syndrome 1. J. Cell Sci. 2011;124:600–612. doi: 10.1242/jcs.077156. PubMed DOI PMC

Chetty-John S., Piwnica-Worms K., Bryant J., Bernardini I., Fischer R.E., Heller T., Gahl W.A., Gunay-Aygun M. Fibrocystic disease of liver and pancreas; under-recognized features of the X-linked ciliopathy oral-facial-digital syndrome type 1 (OFD I) Am. J. Med. Genet. 2010;152:2640–2645. doi: 10.1002/ajmg.a.33666. PubMed DOI PMC

Thauvin-Robinet C., Cossée M., Cormier-Daire V., Van Maldergem L., Toutain A., Alembik Y., Bieth E., Layet V., Parent P., David A., et al. Clinical, molecular, and genotype-phenotype correlation studies from 25 cases of oral-facial-digital syndrome type 1: A French and Belgian collaborative study. J. Med. Genet. 2006;43:54–61. doi: 10.1136/jmg.2004.027672. PubMed DOI PMC

Saal S., Faivre L., Aral B., Gigot N., Toutain A., Van Maldergem L., Destree A., Maystadt I., Cosyns J.-P.P., Jouk P.-S.S., et al. Renal insufficiency, a frequent complication with age in oral-facial-digital syndrome type I. Clin. Genet. 2010;77:258–265. doi: 10.1111/j.1399-0004.2009.01290.x. PubMed DOI

Marina M., Franco B. The molecular basis of oral-facial-digital syndrome, type 1. Am. J. Med. Genet. Part C Semin. Med. Genet. 2009;151:318–325. doi: 10.1002/ajmg.c.30224. PubMed DOI

Zullo A., Iaconis D., Barra A., Cantone A., Messaddeq N., Capasso G., Dollé P., Igarashi P., Franco B. Kidney-specific inactivation of Ofd1 leads to renal cystic disease associated with upregulation of the mTOR pathway. Hum. Mol. Genet. 2010;19:2792–2803. doi: 10.1093/hmg/ddq180. PubMed DOI PMC

Bimonte S., De Angelis A., Quagliata L., Giusti F., Tammaro R., Dallai R., Ascenzi M.-G.G., Diez-Roux G., Franco B. Ofd1 is required in limb bud patterning and endochondral bone development. Dev. Biol. 2011;349:179–191. doi: 10.1016/j.ydbio.2010.09.020. PubMed DOI

Ferrante M.I., Romio L., Castro S., Collins J.E., Goulding D.A., Stemple D.L., Woolf A.S., Wilson S.W. Convergent extension movements and ciliary function are mediated by ofd1, a zebrafish orthologue of the human oral-facial-digital type 1 syndrome gene. Hum. Mol. Genet. 2009;18:289–303. doi: 10.1093/hmg/ddn356. PubMed DOI PMC

Lelièvre H., Chevrier V., Tassin A.-M., Birnbaum D. Myeloproliferative disorder FOP-FGFR1 fusion kinase recruits phosphoinositide-3 kinase and phospholipase Cgamma at the centrosome. Mol. Cancer. 2008;7:30. doi: 10.1186/1476-4598-7-30. PubMed DOI PMC

Delaval B., Létard S., Lelièvre H., Chevrier V., Daviet L., Dubreuil P., Birnbaum D. Oncogenic tyrosine kinase of malignant hemopathy targets the centrosome. Cancer Res. 2005;65:7231–7240. doi: 10.1158/0008-5472.CAN-04-4167. PubMed DOI

Guasch G., Ollendorff V., Borg J.-P., Birnbaum D., Pébusque M.-J. 8p12 Stem Cell Myeloproliferative Disorder: The FOP-Fibroblast Growth Factor Receptor 1 Fusion Protein of the t(6;8) Translocation Induces Cell Survival Mediated by Mitogen-Activated Protein Kinase and Phosphatidylinositol 3-Kinase/Akt/mTOR Pathways. Mol. Cell. Biol. 2001;21:8129–8142. doi: 10.1128/MCB.21.23.8129-8142.2001. PubMed DOI PMC

Guasch G., Delaval B., Arnoulet C., Xie M.J., Xerri L., Sainty D., Birnbaum D., Pébusque M.J. FOP-FGFR1 tyrosine kinase, the product of a t(6;8) translocation, induces a fatal myeloproliferative disease in mice. Blood. 2004;103:309–312. doi: 10.1182/blood-2003-05-1690. PubMed DOI

Mikolajka A., Yan X., Popowicz G.M., Smialowski P., Nigg E.A., Holak T.A. Structure of the N-terminal Domain of the FOP (FGFR1OP) Protein and Implications for its Dimerization and Centrosomal Localization. J. Mol. Biol. 2006;359:863–875. doi: 10.1016/j.jmb.2006.03.070. PubMed DOI

Hori A., Toda T. Regulation of centriolar satellite integrity and its physiology. Cell. Mol. Life Sci. 2016;74:213–229. doi: 10.1007/s00018-016-2315-x. PubMed DOI PMC

Odabasi E., Gul S., Kavakli I.H., Firat-Karalar E.N. Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation. EMBO Rep. 2019;20:1–20. doi: 10.15252/embr.201947723. PubMed DOI PMC

Tollenaere M.A.X., Mailand N., Bekker-Jensen S. Centriolar satellites: Key mediators of centrosome functions. Cell. Mol. Life Sci. 2015;72:11–23. doi: 10.1007/s00018-014-1711-3. PubMed DOI PMC

Bärenz F., Mayilo D., Gruss O.J. Centriolar satellites: Busy orbits around the centrosome. Eur. J. Cell Biol. 2011;90:983–989. doi: 10.1016/j.ejcb.2011.07.007. PubMed DOI

Yan X., Habedanck R., Nigg E.A. A Complex of Two Centrosomal Proteins, CAP350 and FOP, Cooperates with EB1 in Microtubule Anchoring. Mol. Biol. Cell. 2006;17:634–644. doi: 10.1091/mbc.e05-08-0810. PubMed DOI PMC

Mohammadi M., McMahon G., Sun L., Tang C., Hirth P., Yeh B.K., Hubbard S.R., Schlessinger J. Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors. Science. 1997;276:955–960. doi: 10.1126/science.276.5314.955. PubMed DOI

Mohammadi M., Honegger A.M., Rotin D., Fischer R., Bellot F., Li W., Dionne C.A., Jaye M., Rubinstein M., Schlessinger J. A tyrosine-phosphorylated carboxy-terminal peptide of the fibroblast growth factor receptor (Flg) is a binding site for the SH2 domain of phospholipase C-gamma 1. Mol. Cell. Biol. 1991;11:5068–5078. doi: 10.1128/MCB.11.10.5068. PubMed DOI PMC

Lee J.Y., Hong W.J., Majeti R., Stearns T. Centrosome-kinase fusions promote oncogenic signaling and disrupt centrosome function in myeloproliferative neoplasms. PLoS ONE. 2014;9:e92641. doi: 10.1371/journal.pone.0092641. PubMed DOI PMC

Lee J.Y., Stearns T. FOP Is a Centriolar Satellite Protein Involved in Ciliogenesis. PLoS ONE. 2013;8:e58589. doi: 10.1371/journal.pone.0058589. PubMed DOI PMC

Mojarad B.A., Gupta G.D., Hasegan M., Goudiam O., Basto R., Gingras A.C., Pelletier L. CEP19 cooperates with FOP and CEP350 to drive early steps in the ciliogenesis programme. Open Biol. 2017;7 doi: 10.1098/rsob.170114. PubMed DOI PMC

Cabaud O., Roubin R., Comte A., Bascunana V., Sergé A., Sedjaï F., Birnbaum D., Rosnet O., Acquaviva C. Mutation of FOP/FGFR1OP in mice recapitulates human short rib-polydactyly ciliopathy. Hum. Mol. Genet. 2018;27:3377–3391. doi: 10.1093/hmg/ddy246. PubMed DOI

Bangs F., Anderson K.V. Primary Cilia and Mammalian Hedgehog Signaling. Cold Spring Harb. Perspect. Biol. 2017;9:a028175. doi: 10.1101/cshperspect.a028175. PubMed DOI PMC

Satir P., Christensen S.T. Overview of Structure and Function of Mammalian Cilia. Annu. Rev. Physiol. 2007;69:377–400. doi: 10.1146/annurev.physiol.69.040705.141236. PubMed DOI

Giehl M., Fabarius A., Frank O., Hochhaus A., Hafner M., Hehlmann R., Seifarth W. Centrosome aberrations in chronic myeloid leukemia correlate with stage of disease and chromosomal instability. Leukemia. 2005;19:1192–1197. doi: 10.1038/sj.leu.2403779. PubMed DOI

Ren M., Qin H., Kitamura E., Cowell J.K. Dysregulated signaling pathways in the development of CNTRL-FGFR1-induced myeloid and lymphoid malignancies associated with FGFR1 in human and mouse models. Blood. 2013;122:1007–1016. doi: 10.1182/blood-2013-03-489823. PubMed DOI PMC

Ren M., Qin H., Ren R., Tidwell J., Cowell J.K. Src activation plays an important key role in lymphomagenesis induced by FGFR1 fusion kinases. Cancer Res. 2011;71:7312–7322. doi: 10.1158/0008-5472.CAN-11-1109. PubMed DOI PMC

Arber D.A., Orazi A., Hasserjian R., Thiele J., Borowitz M.J., Le Beau M.M., Bloomfield C.D., Cazzola M., Vardiman J.W. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–2405. doi: 10.1182/blood-2016-03-643544. PubMed DOI

Ren M., Qin H., Ren R., Cowell J.K. Ponatinib suppresses the development of myeloid and lymphoid malignancies associated with FGFR1 abnormalities. Leukemia. 2013;27:32–40. doi: 10.1038/leu.2012.188. PubMed DOI PMC

Ou Y.Y., Mack G.J., Zhang M., Rattner J.B. CEP110 and ninein are located in a specific domain of the centrosome associated with centrosome maturation. J. Cell Sci. 2002;115:1825–1835. doi: 10.1242/jcs.115.9.1825. PubMed DOI

Kashihara H., Chiba S., Kanno S.-I., Suzuki K., Yano T., Tsukita S. Cep128 associates with Odf2 to form the subdistal appendage of the centriole. Genes Cells. 2019;24:231–243. doi: 10.1111/gtc.12668. PubMed DOI

Sun T.-Y., Wang H.-Y., Kwon J.-W., Yuan B., Lee I.-W., Cui X.-S., Kim N.-H. Centriolin, a centriole-appendage protein, regulates peripheral spindle migration and asymmetric division in mouse meiotic oocytes. Cell Cycle. 2017;16:1774–1780. doi: 10.1080/15384101.2016.1264544. PubMed DOI PMC

Chen C.-T., Hehnly H., Yu Q., Farkas D., Zheng G., Redick S.D., Hung H.-F., Samtani R., Jurczyk A., Akbarian S., et al. A unique set of centrosome proteins requires pericentrin for spindle-pole localization and spindle orientation. Curr. Biol. 2014;24:2327–2334. doi: 10.1016/j.cub.2014.08.029. PubMed DOI PMC

Lassman A.B., Sepúlveda-Sánchez J.M., Cloughesy T., Gil-Gil J.M., Puduvalli V.K., Raizer J., De Vos F.Y., Wen P.Y., Butowski N., Clement P., et al. OS10.6 Infigratinib (BGJ398) in patients with recurrent gliomas with fibroblast growth factor receptor (FGFR) alterations: A multicenter phase II study. Neuro. Oncol. 2019;21:iii21–iii22. doi: 10.1093/neuonc/noz126.072. DOI

Goyal L., Shi L., Liu L.Y., de la Cruz F.F., Lennerz J.K., Raghavan S., Leschiner I., Elagina L., Siravegna G., Ng R.W.S., et al. TAS-120 overcomes resistance to atp-competitive FGFR inhibitors in patients with FGFR2 fusion–positive intrahepatic cholangiocarcinoma. Cancer Discov. 2019;9:1064–1079. doi: 10.1158/2159-8290.CD-19-0182. PubMed DOI PMC

Krzyscik M.A., Zakrzewska M., Otlewski J. Site-Specific, Stoichiometric-Controlled, PEGylated Conjugates of Fibroblast Growth Factor 2 (FGF2) with Hydrophilic Auristatin y for Highly Selective Killing of Cancer Cells Overproducing Fibroblast Growth Factor Receptor 1 (FGFR1) Mol. Pharm. 2020;17:2734–2748. doi: 10.1021/acs.molpharmaceut.0c00419. PubMed DOI PMC

Porębska N., Latko M., Kucińska M., Zakrzewska M., Otlewski J., Opaliński Ł. Targeting Cellular Trafficking of Fibroblast Growth Factor Receptors as a Strategy for Selective Cancer Treatment. J. Clin. Med. 2018;8:7. doi: 10.3390/jcm8010007. PubMed DOI PMC

Canning P., Park K., Gonçalves J., Li C., Howard C.J., Sharpe T.D., Holt L.J., Pelletier L., Bullock A.N., Leroux M.R. CDKL Family Kinases Have Evolved Distinct Structural Features and Ciliary Function. Cell Rep. 2018;22:885–894. doi: 10.1016/j.celrep.2017.12.083. PubMed DOI PMC

Harrington K.J., Hingorani M., Tanay M.A., Hickey J., Bhide S.A., Clarke P.M., Renouf L.C., Thway K., Sibtain A., McNeish I.A., et al. Phase I/II study of oncolytic HSVGM-CSFin combination with radiotherapy and cisplatin in untreated stage III/IV squamous cell cancer of the head and neck. Clin. Cancer Res. 2010;16:4005–4015. doi: 10.1158/1078-0432.CCR-10-0196. PubMed DOI

Heo J., Reid T., Ruo L., Breitbach C.J., Rose S., Bloomston M., Cho M., Lim H.Y., Chung H.C., Kim C.W., et al. Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer. Nat. Med. 2013;19:329–336. doi: 10.1038/nm.3089. PubMed DOI PMC

Freytag S.O., Stricker H., Lu M., Elshaikh M., Aref I., Pradhan D., Levin K., Kim J.H., Peabody J., Siddiqui F., et al. Prospective randomized phase 2 trial of intensity modulated radiation therapy with or without oncolytic adenovirus-mediated cytotoxic gene therapy in intermediate-risk prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 2014;89:268–276. doi: 10.1016/j.ijrobp.2014.02.034. PubMed DOI PMC

Ronca R., Giacomini A., Di Salle E., Coltrini D., Pagano K., Ragona L., Matarazzo S., Rezzola S., Maiolo D., Torrella R., et al. Long-Pentraxin 3 Derivative as a Small-Molecule FGF Trap for Cancer Therapy. Cancer Cell. 2015;28:225–239. doi: 10.1016/j.ccell.2015.07.002. PubMed DOI

FGFR2 residence in primary cilia is necessary for epithelial cell signaling