title: Point mutation within the tyrosine kinase domain of the RET proto-oncogene in multiple endocrine neoplasia type 2B and related sporadic tumours.
abstract: The susceptibility loci for the three multiple endocrine neoplasia (MEN) type 2 syndromes have been mapped to the region of chromosome 10q11.2 containing the RET proto-oncogene, which codes for a receptor tyrosine kinase. The majority of MEN 2A and familial medullary thyroid carcinoma results from missense mutations within one of five cysteine codons in the extracellular domain of the RET proto-oncogene. We now report a missense mutation, resulting in the substitution of a threonine for a methionine at codon 918 in the tyrosine kinase catalytic domain, in the germline of 26 of 28 apparently distinct families with MEN 2B. DNA from five of 13 apparently sporadic MTC and one of 12 apparently sporadic phaeochromocytomas harboured a similar mutation, but the corresponding germline DNA was wildtype in each case.
authors.affiliation: Department of Pathology, University of Cambridge, UK.
authors.forename: C
authors.initials: C
authors.lastname: Eng
authors.forename: D P
authors.initials: DP
authors.lastname: Smith
authors.forename: L M
authors.initials: LM
authors.lastname: Mulligan
authors.forename: M A
authors.initials: MA
authors.lastname: Nagai
authors.forename: C S
authors.initials: CS
authors.lastname: Healey
authors.forename: M A
authors.initials: MA
authors.lastname: Ponder
authors.forename: E
authors.initials: E
authors.lastname: Gardner
authors.forename: G F
authors.initials: GF
authors.lastname: Scheumann
authors.forename: C E
authors.initials: CE
authors.lastname: Jackson
authors.forename: A
authors.initials: A
authors.lastname: Tunnacliffe
mesh_terms: D000236:Adenoma / Q000235:genetics; D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000483:Alleles; D001483:Base Sequence; D018276:Carcinoma, Medullary / Q000235:genetics*; D003062:Codon; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D029721:Drosophila Proteins; D005091:Exons; D006627:Hirschsprung Disease / Q000235:genetics*; D006965:Hyperplasia; D008969:Molecular Sequence Data; D009377:Multiple Endocrine Neoplasia / Q000235:genetics*; D010280:Parathyroid Glands / Q000473:pathology; D010282:Parathyroid Neoplasms / Q000235:genetics; D010673:Pheochromocytoma / Q000235:genetics*; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D011519:Proto-Oncogenes; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: D003062:Codon; D004273:DNA, Neoplasm; D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila