title: Receptor tyrosine kinase mutations in developmental syndromes and cancer: two sides of the same coin.
abstract: Receptor tyrosine kinases (RTKs) are a family of ligand-binding cell surface receptors that regulate a wide range of essential cellular activities, including proliferation, differentiation, cell-cycle progression, survival and apoptosis. As such, these proteins play an important role during development and throughout life; germline mutations in genes encoding RTKs cause several developmental syndromes, while somatic alterations contribute to the pathogenesis of many aggressive cancers. This creates an interesting paradigm in which mutation timing, type and location in a gene leads to different cell signaling and biological responses, and ultimately phenotypic outcomes. In this review, we highlight the roles of RTKs in developmental disorders and cancer. The multifaceted roles of these receptors, their genetic signatures and their signaling during developmental morphogenesis and oncogenesis are discussed. Additionally, we propose that comparative analysis of RTK mutations responsible for developmental syndromes may shed light on those driving tumorigenesis.
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Laura M
authors.initials: LM
authors.lastname: McDonell
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Kristin D
authors.initials: KD
authors.lastname: Kernohan
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada kboycott@cheo.on.ca.
authors.forename: Kym M
authors.initials: KM
authors.lastname: Boycott
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Sawyer
mesh_terms: D063646:Carcinogenesis / Q000235:genetics; D047108:Embryonic Development; D006801:Humans; D009024:Morphogenesis / Q000235:genetics; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D013577:Syndrome
chemical_list: D020794:Receptor Protein-Tyrosine Kinases