title: RET and NTRK1 proto-oncogenes in human diseases.
abstract: RET and NTRK1 are receptor tyrosine kinase (RTK) proteins which play a role in the development and maturation of specific component of the nervous system. Their alterations have been associated to several human diseases, including some forms of cancer and developmental abnormalities. These features have contributed to the concept that one gene can be responsible for more than one disease. Moreover, both genes encoding for the two RTKs show genetic alterations that belong to either "gain of function" or "loss of function" class of mutations. In fact, receptor rearrangements or point mutations convert RET and NTRK1 in dominantly acting transforming genes leading to thyroid tumors, whereas inactivating mutations, associated with Hirschsprung's disease (HSCR) and congenital insensitivity to pain with anhidrosis (CIPA), impair RET and NTRK1 functions, respectively. In this review we have summarized the main features of the two receptors, their physiological and pathological roles. In addition, we attempted to identify the correlations between the different genetic alterations and the related pathogenetic mechanisms.
authors.affiliation: Operative Unit Molecular Mechanisms of Tumor Growth and Progression, Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Luisella
authors.initials: L
authors.lastname: Alberti
authors.forename: Cristiana
authors.initials: C
authors.lastname: Carniti
authors.forename: Claudia
authors.initials: C
authors.lastname: Miranda
authors.forename: Emanuela
authors.initials: E
authors.lastname: Roccato
authors.forename: Marco A
authors.initials: MA
authors.lastname: Pierotti
mesh_terms: D000818:Animals; D029721:Drosophila Proteins; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006627:Hirschsprung Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D009154:Mutation / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D020917:Receptor, trkA / Q000235:genetics* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
chemical_list: D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; C416649:Ret protein, Drosophila