title: Double germline mutations in the RET Proto-oncogene in MEN 2A and MEN 2B kindreds.
abstract: Medullary thyroid carcinoma (MTC) is a rare form of thyroid cancer representing about 10% of all thyroid malignancies. It occurs mostly as a sporadic tumor or in association with autosomal dominant inherited cancer syndromes--multiple endocrine neoplasia (MEN) types 2A and 2B and familial MTC. Germline mutations in exons 8, 10, 11, 13, 14, 15 and 16 of the RET proto-oncogene are found in most of the familial cases. There are only a few published data reporting multiple germline mutations in the RET proto-oncogene. We have detected double germline mutations in 2 different exons on the same RET allele in two MEN 2 families. In the MEN 2A family, double germline mutation in exons 10 (Cys620Phe) and 13 (Tyr791Phe) was detected. In the MEN 2B family, beside the classical germline mutation in exon 16 (Met918Thr) a second germline mutation in exon 13 (Tyr791Phe) was found. This study revealed that MEN 2 syndromes can also be caused by double germline mutations in the RET proto-oncogene and these families can be added to small worldwide cohort of families with multiple germline mutations.
authors.affiliation: Institute of Endocrinology, Department of Endokrinology, Prague 1, Czech Republic. sarka@obloha.cz
authors.forename: S
authors.initials: S
authors.lastname: Dvorakova
authors.forename: E
authors.initials: E
authors.lastname: Vaclavikova
authors.forename: A
authors.initials: A
authors.lastname: Ryska
authors.forename: J
authors.initials: J
authors.lastname: Cap
authors.forename: P
authors.initials: P
authors.lastname: Vlcek
authors.forename: J
authors.initials: J
authors.lastname: Duskova
authors.forename: D
authors.initials: D
authors.lastname: Kodetova
authors.forename: V
authors.initials: V
authors.lastname: Holub
authors.forename: Z
authors.initials: Z
authors.lastname: Novak
authors.forename: B
authors.initials: B
authors.lastname: Bendlova
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D015331:Cohort Studies; D005091:Exons / Q000235:genetics; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D018814:Multiple Endocrine Neoplasia Type 2b / Q000235:genetics*; D010375:Pedigree; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret