title: A Korean family of familial medullary thyroid cancer with Cys618Ser RET germline mutation.
abstract: Familial medullary thyroid carcinoma (FMTC) is caused by autosomal dominant gain-of-function mutations in the RET proto-oncogene. An identifiable RET mutation can be detected in about 85% of FMTC families. The majority of germline mutations in FMTC have been found in exons 10 and 11 of the RET proto-oncogene, specifically within the cysteine codons 609, 611, 618, 620, and 634. We screened members of a large Korean family that had a history of FMTC by genetic analyses, and propose a therapeutic approach for managing the disorder. We report a RET mutation in exon10, codon 618 that causes substitution of a cysteine by a serine in the cysteine-rich domain of the RET receptor in a three-generation FMTC family composed of 30 members with 11 carriers. Nine of the gene carriers were clinically affected. The FMTC with cysteine RET mutations found in the Korean population is consistent with the clinical pattern reported worldwide; to date there have been no ethnic differences identified for FMTC. Our results suggest that this genetic profile might be associated with usually aggressive clinical course with regional lymph node metastasis but late onset of MTC.
authors.affiliation: Department of Surgery, Kyungpook National University Hospital, Daegu, Korea.
authors.forename: Jinhyang
authors.initials: J
authors.lastname: Jung
authors.forename: Shinya
authors.initials: S
authors.lastname: Uchino
authors.forename: Youngha
authors.initials: Y
authors.lastname: Lee
authors.forename: Hoyong
authors.initials: H
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D018276:Carcinoma, Medullary / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D056910:Republic of Korea; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret