title: Novel germline RET proto-oncogene mutations associated with medullary thyroid carcinoma (MTC): mutation analysis in Japanese patients with MTC.
abstract: Germ-like and somatic mutations in the RET proto-oncogene are associated with inherited and sporadic medullary thyroid carcinoma (MTC). The majority of patients with multiple endocrine neoplasia type 2A (MEN2A) and familial medullary thyroid carcinoma (FMTC) carry germ-line point mutations that result in the substitution of one of five cysteine residues. We investigated exons 10, 11, 13, 14 and 16 of the RET proto-oncogene in 33 unrelated Japanese patients with MTC. Eleven of the 33 cases (33%) were found to have germ-line mutations. Three previously unreported mutations in exon 10 and 11 were identified: one in codon 620, (TGC-->GGC), resulting in a cysteine to glycine substitution, and two in codon 630, (TGC-->TCC) and (TGC-->TAC), resulting in cysteine to serine and cysteine to tyrosine changes, respectively. The new mutations were present in the germ-line DNA of four unrelated patients for whom a family history of MTC had not been documented. Because the new RET alleles described here involve cysteine residues in a region of protein previously associated with FMTC and MEN2A, it is very likely that they represent mutations that predispose to the development of MTC.
authors.affiliation: Department of Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Kitamura
authors.forename: P J
authors.initials: PJ
authors.lastname: Goodfellow
authors.forename: K
authors.initials: K
authors.lastname: Shimizu
authors.forename: M
authors.initials: M
authors.lastname: Nagahama
authors.forename: K
authors.initials: K
authors.lastname: Ito
authors.forename: W
authors.initials: W
authors.lastname: Kitagawa
authors.forename: H
authors.initials: H
authors.lastname: Akasu
authors.forename: H
authors.initials: H
authors.lastname: Takami
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
authors.forename: S A
authors.initials: SA
authors.lastname: Wells
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018276:Carcinoma, Medullary / Q000235:genetics*; D004252:DNA Mutational Analysis; D029721:Drosophila Proteins; D018095:Germ-Line Mutation; D006801:Humans; D007564:Japan; D008875:Middle Aged; D018807:Polymorphism, Single-Stranded Conformational; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: 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