title: Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A.
abstract: Multiple endocrine neoplasia type 2A (MEN 2A) is a dominantly inherited cancer syndrome that affects tissues derived from neural ectoderm. It is characterized by medullary thyroid carcinoma (MTC) and phaeochromocytoma. The MEN2A gene has recently been localized by a combination of genetic and physical mapping techniques to a 480-kilobase region in chromosome 10q11.2 (refs 2,3). The DNA segment encompasses the RET proto-oncogene, a receptor tyrosine kinase gene expressed in MTC and phaeochromocytoma and at lower levels in normal human thyroid. This suggested RET as a candidate for the MEN2A gene. We have identified missense mutations of the RET proto-oncogene in 20 of 23 apparently distinct MEN 2A families, but not in 23 normal controls. Further, 19 of these 20 mutations affect the same conserved cysteine residue at the boundary of the RET extracellular and transmembrane domains.
authors.affiliation: Department of Pathology, University of Cambridge, UK.
authors.forename: L M
authors.initials: LM
authors.lastname: Mulligan
authors.forename: J B
authors.initials: JB
authors.lastname: Kwok
authors.forename: C S
authors.initials: CS
authors.lastname: Healey
authors.forename: M J
authors.initials: MJ
authors.lastname: Elsdon
authors.forename: C
authors.initials: C
authors.lastname: Eng
authors.forename: E
authors.initials: E
authors.lastname: Gardner
authors.forename: D R
authors.initials: DR
authors.lastname: Love
authors.forename: S E
authors.initials: SE
authors.lastname: Mole
authors.forename: J K
authors.initials: JK
authors.lastname: Moore
authors.forename: L
authors.initials: L
authors.lastname: Papi
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002277:Carcinoma / Q000235:genetics; D003062:Codon; D003545:Cysteine / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004277:DNA, Single-Stranded; D029721:Drosophila Proteins; D005854:Germ Cells; D006579:Heterozygote; D006801:Humans; D008969:Molecular Sequence Data; D009377:Multiple Endocrine Neoplasia / Q000235:genetics*; D009154:Mutation; D010673:Pheochromocytoma / Q000235:genetics; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D011519:Proto-Oncogenes; D020794:Receptor Protein-Tyrosine Kinases; D013964:Thyroid Neoplasms / Q000235:genetics
chemical_list: D003062:Codon; D004273:DNA, Neoplasm; D004277:DNA, Single-Stranded; D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; D003545:Cysteine