title: Functions of Fibroblast Growth Factor Receptors in cancer defined by novel translocations and mutations.
abstract: The four receptor tyrosine kinases (RTKs) within the family of Fibroblast Growth Factor Receptors (FGFRs) are critical for normal development but also play an enormous role in oncogenesis. Mutations and/or abnormal expression often lead to constitutive dimerization and kinase activation of FGFRs, and represent the primary mechanism for aberrant signaling. Sequencing of human tumors has revealed a plethora of somatic mutations in FGFRs that are frequently identical to germline mutations in developmental syndromes, and has also identified novel FGFR fusion proteins arising from chromosomal rearrangements that contribute to malignancy. This review details approximately 200 specific point mutations in FGFRs and 40 different fusion proteins created by translocations involving FGFRs that have been identified in human cancer. This review discusses the effects of these genetic alterations on downstream signaling cascades, and the challenge of drug resistance in cancer treatment with antagonists of FGFRs.
authors.affiliation: Department of Chemistry and Biochemistry, Moores UCSD Cancer Center, University of California San Diego, La Jolla, CA 92093-0367, United States. Electronic address: legallo@ucsd.edu.
authors.forename: Leandro H
authors.initials: LH
authors.lastname: Gallo
authors.affiliation: Department of Chemistry and Biochemistry, Moores UCSD Cancer Center, University of California San Diego, La Jolla, CA 92093-0367, United States. Electronic address: kanelson@ucsd.edu.
authors.forename: Katelyn N
authors.initials: KN
authors.lastname: Nelson
authors.affiliation: Department of Chemistry and Biochemistry, Moores UCSD Cancer Center, University of California San Diego, La Jolla, CA 92093-0367, United States. Electronic address: ameyer@ucsd.edu.
authors.forename: April N
authors.initials: AN
authors.lastname: Meyer
authors.affiliation: Department of Chemistry and Biochemistry, Moores UCSD Cancer Center, University of California San Diego, La Jolla, CA 92093-0367, United States. Electronic address: ddonoghue@ucsd.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Donoghue
mesh_terms: D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D015398:Signal Transduction; D014178:Translocation, Genetic
chemical_list: D017468:Receptors, Fibroblast Growth Factor
keywords: Development; Fibroblast Growth Factor Receptor; Myeloproliferative syndrome; Rhabdomyosarcoma; Translocation