title: A novel point mutation in the intracellular domain of the ret protooncogene in a family with medullary thyroid carcinoma.
abstract: Specific mutations in the ret protooncogene have been found associated with multiple endocrine neoplasia type 2A (MEN 2A) and type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC). Mutations in one of five cysteine residues in the extracellular domain have been found in over 95% of families with MEN 2A and 88% of families with FMTC. In MEN 2B patients, a specific mutation at codon 918, substituting a threonine for a methionine, has been found in 95% of cases. In FMTC, in addition to the mutations of the extracellular cysteines, three intracellular base pair changes have been reported at codons 768 and 804. Here we describe a novel intracellular mutation in exon 15 of the ret gene that leads to the substitution of an alanine for a serine at codon 891 in a family with medullary thyroid carcinoma. This amino acid change may be important in determining substrate specificity or, alternatively, may play a role in ATP binding.
authors.affiliation: Department of Medical Genetics, University of Groningen, The Netherlands. R.M.W.Hofstra@med.rug.nl
authors.forename: R M
authors.initials: RM
authors.lastname: Hofstra
authors.forename: O
authors.initials: O
authors.lastname: Fattoruso
authors.forename: L
authors.initials: L
authors.lastname: Quadro
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: A
authors.initials: A
authors.lastname: Libroia
authors.forename: U
authors.initials: U
authors.lastname: Verga
authors.forename: V
authors.initials: V
authors.lastname: Colantuoni
authors.forename: C H
authors.initials: CH
authors.lastname: Buys
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D018276:Carcinoma, Medullary / Q000235:genetics*; D029721:Drosophila Proteins; D005091:Exons / Q000235:genetics; D005110:Extracellular Space / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D011519:Proto-Oncogenes / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila