title: Current concepts in RET-related genetics, signaling and therapeutics.
abstract: The receptor tyrosine kinase RET is expressed in cell lineages derived from the neural crest and has a key role in regulating cell proliferation, migration, differentiation and survival during embryogenesis. Germline and somatic mutations in RET that produce constitutively activated receptors cause the cancer syndrome multiple endocrine neoplasia type 2 and several endocrine and neural-crest-derived tumors, whereas mutations resulting in nonfunctional RET or lower expression of RET are found in individuals affected with Hirschsprung disease. This review focuses on the genetics and molecular mechanisms underlying the different inherited human neural-crest-related disorders in which RET dysfunction has a crucial role and discusses RET as a potential therapeutic target.
authors.affiliation: Department of Genetics, University Medical Center Groningen, University of Groningen, Postbus 30 001, 9700 RB Groningen, The Netherlands.
authors.forename: Ivan
authors.initials: I
authors.lastname: Plaza-Menacho
authors.forename: Grzegorz M
authors.initials: GM
authors.lastname: Burzynski
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: de Groot
authors.forename: Bart J L
authors.initials: BJ
authors.lastname: Eggen
authors.forename: Robert M W
authors.initials: RM
authors.lastname: Hofstra
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D006239:Haplotypes; D006627:Hirschsprung Disease / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D041681:NIH 3T3 Cells; D011110:Polymorphism, Genetic; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human