title: A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma.
abstract: Multiple endocrine neoplasia type 2 (MEN 2) comprises three clinically distinct, dominantly inherited cancer syndromes. MEN 2A patients develop medullary thyroid carcinoma (MTC) and phaeochromocytoma. MEN 2B patients show in addition ganglioneuromas of the gastrointestinal tract and skeletal abnormalities. In familial MTC, only the thyroid is affected. Germ-line mutations of the RET proto-oncogene have recently been reported in association with MEN 2A and familial MTC. All mutations occurred within codons specifying cysteine residues in the transition point between the RET protein extracellular and transmembrane domains. We now show that MEN 2B is also associated with mutation of the RET proto-oncogene. A mutation in codon 664, causing the substitution of a threonine for a methionine in the tyrosine kinase domain of the protein, was found in all nine unrelated MEN 2B patients studied. The same mutation was found in six out of 18 sporadic tumours.
authors.affiliation: Department of Medical Genetics, University of Groningen, The Netherlands.
authors.forename: R M
authors.initials: RM
authors.lastname: Hofstra
authors.forename: R M
authors.initials: RM
authors.lastname: Landsvater
authors.forename: I
authors.initials: I
authors.lastname: Ceccherini
authors.forename: R P
authors.initials: RP
authors.lastname: Stulp
authors.forename: T
authors.initials: T
authors.lastname: Stelwagen
authors.forename: Y
authors.initials: Y
authors.lastname: Luo
authors.forename: B
authors.initials: B
authors.lastname: Pasini
authors.forename: J W
authors.initials: JW
authors.lastname: Höppener
authors.forename: H K
authors.initials: HK
authors.lastname: van Amstel
authors.forename: G
authors.initials: G
authors.lastname: Romeo
mesh_terms: D001483:Base Sequence; D018276:Carcinoma, Medullary / Q000201:enzymology / Q000235:genetics*; D003062:Codon; D017931:DNA Primers; D029721:Drosophila Proteins; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009377:Multiple Endocrine Neoplasia / Q000201:enzymology / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; 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 / Q000201:enzymology / Q000235:genetics*
chemical_list: D003062:Codon; D017931:DNA Primers; 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