title: RET and neuroendocrine tumors.
abstract: The RET proto-oncogene encodes a receptor tyrosine kinase that is a main component of the signaling pathway activated by the glial cell line-derived neurotrophic factor family ligands. Gene targeting studies revealed that signaling through RET plays a crucial role in neuronal and renal organogenesis. It is well-known that germline mutations in RET lead to the human inherited diseases, multiple endocrine neoplasia type 2 (MEN 2) and Hirschsprung's disease, and that somatic rearrangements of RET cause papillary thyroid carcinoma. Due to marked advances in understanding of the molecular mechanisms of the development of MEN 2, a consensus on MEN 2 management associated with RET status is being reached and currently put into general use as a guideline. In this review, we summarize progress in the study of RET from bench to bedside, focusing on pathophysiology of neuroendocrine tumors.
authors.affiliation: Department of Pathology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. murakumo@med.nagoya-u.ac.jp
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Murakumo
authors.forename: Mayumi
authors.initials: M
authors.lastname: Jijiwa
authors.forename: Naoya
authors.initials: N
authors.lastname: Asai
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ichihara
authors.forename: Masahide
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000201:enzymology; D000818:Animals; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018276:Carcinoma, Medullary / Q000201:enzymology; D002291:Carcinoma, Papillary / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018813:Multiple Endocrine Neoplasia Type 2a / Q000201:enzymology; D018814:Multiple Endocrine Neoplasia Type 2b / Q000201:enzymology; D009154:Mutation; D018358:Neuroendocrine Tumors / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D010673:Pheochromocytoma / Q000201:enzymology; D011379:Prognosis; D011487:Protein Conformation; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013964:Thyroid Neoplasms / Q000201:enzymology
chemical_list: D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human