title: Germline and somatic mutations of the RET proto-oncogene in apparently sporadic medullary thyroid carcinomas.
abstract: Medullary thyroid carcinomas (MTC) occur sporadically or as part of inherited multiple endocrine neoplasia (MEN) type 2 syndromes. To recognize misdiagnosed familial cases and to establish the frequency of somatic mutations, a series of 50 patients, clinically diagnosed with sporadic MTC, were analyzed for mutations in the RET proto-oncogene. The clinical management of the patient and of the family is different in the two cases. Germline mutations were detected in three independent cases, demonstrating that they were associated to familial MTC. The mutations affected exon 11 in two cases and exon 14 in one case. Somatic mutations were detected in eight patients (30%) and they were indicative of sporadic MTC. In seven cases the mutation affected codon 918 of exon 16 and in one case codon 634 in exon 11. No RET mutations were detected in the remaining patients. A different genetic and clinical management is proposed for individuals with a diagnosis of familial or sporadic MTC.
authors.affiliation: Istituto di Endocrinologia, Facoltà di Medicina, Seconda Università di Napoli, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Scurini
authors.forename: L
authors.initials: L
authors.lastname: Quadro
authors.forename: O
authors.initials: O
authors.lastname: Fattoruso
authors.forename: U
authors.initials: U
authors.lastname: Verga
authors.forename: A
authors.initials: A
authors.lastname: Libroia
authors.forename: G
authors.initials: G
authors.lastname: Lupoli
authors.forename: E
authors.initials: E
authors.lastname: Cascone
authors.forename: L
authors.initials: L
authors.lastname: Marzano
authors.forename: S
authors.initials: S
authors.lastname: Paracchi
authors.forename: B
authors.initials: B
authors.lastname: Busnardo
authors.forename: M E
authors.initials: ME
authors.lastname: Girelli
authors.forename: A
authors.initials: A
authors.lastname: Bellastella
authors.forename: V
authors.initials: V
authors.lastname: Colantuoni
mesh_terms: D018276:Carcinoma, Medullary / Q000235:genetics*; D029721:Drosophila Proteins; D018095:Germ-Line Mutation; D006801:Humans; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics; D009154:Mutation; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D011519:Proto-Oncogenes; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila