title: Molecular genetics and phenomics of RET mutations: Impact on prognosis of MTC.
abstract: Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant hereditary cancer syndrome caused by missense gain-of-function mutations of the RET proto-oncogene. Three distinct clinical subtypes of MEN 2 have been characterized: MEN 2A, MEN 2B, and familial medullary thyroid carcinoma (FMTC). The specific RET mutation may suggest a predilection toward a particular phenotype and clinical course, with strong genotype-phenotype correlations. Recommendations on the timing of prophylactic thyroidectomy and extent of surgery are based on classification of RET mutations into risk levels according to genotype-phenotype correlations. The excellent prognosis for MTC diagnosed at its earliest stage underscores the importance of prospective screening (calcitonin screening) for sporadic MTC and early diagnosis by RET-mutation analysis for hereditary MTC. MEN 2 provides a unique model for early prevention and cure of cancer and for the roles of stratified mutation-based diagnosis and therapy of carriers.
authors.affiliation: Endocrine Practice, Molecular Laboratory, Brueckenstr. 21, Heidelberg 69120, Germany. karin.frankraue@raue-endokrinologie.de
authors.forename: Karin
authors.initials: K
authors.lastname: Frank-Raue
authors.forename: Susanne
authors.initials: S
authors.lastname: Rondot
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Raue
mesh_terms: D018276:Carcinoma, Medullary / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D018814:Multiple Endocrine Neoplasia Type 2b / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human