title: Germline and somatic mutations in an oncogene: RET mutations in inherited medullary thyroid carcinoma.
abstract: Inherited cancer syndromes predispose an individual to development of specific tumors. Somatic and germline mutations in the same tumor suppressor gene, as described in Knudson's two-mutation model, are well recognized. Inherited mutations in the RET proto-oncogene, which encodes a receptor tyrosine kinase, predispose individuals to the multiple endocrine neoplasia type 2 (MEN 2) cancer syndromes. The major component tumor of these syndromes is medullary thyroid carcinoma (MTC). To date, somatic mutations in RET have not been identified in tumors from individuals with MEN 2, although they have been well documented in sporadic MEN 2-related tumors. We have identified, among 16 MEN 2 cases with well-defined RET germline mutations, a somatic missense mutation at codon 918 of RET in 3 of 15 MTCs and in a sample with hyperplastic C-cells (presumed precursor to hereditary MTC). We suggest that the presence of a somatic mutation, in addition to the preexisting germline mutation in hereditary MTCs, may contribute to tumorigenesis in vivo.
authors.affiliation: Kolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards, N.S.W., Australia.
authors.forename: D J
authors.initials: DJ
authors.lastname: Marsh
authors.forename: S D
authors.initials: SD
authors.lastname: Andrew
authors.forename: C
authors.initials: C
authors.lastname: Eng
authors.forename: D L
authors.initials: DL
authors.lastname: Learoyd
authors.forename: A G
authors.initials: AG
authors.lastname: Capes
authors.forename: R
authors.initials: R
authors.lastname: Pojer
authors.forename: A L
authors.initials: AL
authors.lastname: Richardson
authors.forename: C
authors.initials: C
authors.lastname: Houghton
authors.forename: L M
authors.initials: LM
authors.lastname: Mulligan
authors.forename: B A
authors.initials: BA
authors.lastname: Ponder
authors.forename: B G
authors.initials: BG
authors.lastname: Robinson
mesh_terms: D018276:Carcinoma, Medullary / Q000235:genetics* / Q000473:pathology; D003062:Codon / Q000235:genetics; D005091:Exons / Q000235:genetics; D005192:Family Health; D006801:Humans; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D003062:Codon; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas