title: Mutation of RET codon 768 is associated with the FMTC phenotype.
abstract: Multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B), and familial medullary thyroid carcinoma (FMTC) are inherited cancer syndromes resulting from mutations in the RET proto-oncogene. Missense mutations of five codons in exons 10 and 11 are found in both MEN 2A and FMTC families, while mutations at codon 768 in exon 13 have been identified in three FMTC families. We report here the results of mutation analysis on a large multi-generation family with multiple cases of medullary thyroid carcinoma (MTC) or C-cell hyperplasia and two individuals with isolated adrenal medullary hyperplasia. A mutation in exon 13, which alters codon 768 from a GAG (Glu) to a GAC (Asp), was found to segregate with the FMTC phenotype in this family but not with the adrenal medullary hyperplasia. These findings suggest that the codon 768 mutation does not predispose to adrenal medullary hyperplasia, but is an accurate predictor of the MTC phenotype in this family.
authors.affiliation: Department of Pathology, Queen's University, Kingston, Ontario, Canada.
authors.forename: L M
authors.initials: LM
authors.lastname: Boccia
authors.forename: J S
authors.initials: JS
authors.lastname: Green
authors.forename: C
authors.initials: C
authors.lastname: Joyce
authors.forename: C
authors.initials: C
authors.lastname: Eng
authors.forename: S A
authors.initials: SA
authors.lastname: Taylor
authors.forename: L M
authors.initials: LM
authors.lastname: Mulligan
mesh_terms: D018276:Carcinoma, Medullary / Q000235:genetics*; D003062:Codon; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D029721:Drosophila Proteins; D005260:Female; D006801:Humans; D008297:Male; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D003062:Codon; 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; C024669:endodeoxyribonuclease AluI; D015252:Deoxyribonucleases, Type II Site-Specific