title: Relevance of RET proto-oncogene mutations in sporadic medullary thyroid carcinoma.
abstract: Analysis of peripheral blood or tumor DNA samples from 101 patients with apparent sporadic medullary thyroid carcinoma (MTC) was performed to assess the frequency of RET proto-oncogene mutations in this patient population. Peripheral blood and/or tumor DNA was amplified by polymerase chain reaction. DNA sequence or restriction enzyme analysis was performed to detect mutations of RET proto-oncogene codons 609, 611, 618, 620, 634, 768, and 918. Six of 101 patients with apparent sporadic MTC had peripheral blood DNA mutations more commonly associated with hereditary MTC. In 4 patients, these mutations led to the identification of previously unrecognized kindreds. The remaining 2 patients were examples of de novo mutations. A codon 918 mutation was found in 14 of 57 (approximately 25%) tumor DNA samples. Mutations were not identified in the remaining patients. In this large cancer center population, approximately 6% of patients with sporadic MTC carry peripheral blood DNA mutations, either inherited or de novo, more commonly associated with MEN 2A or familial MTC. Seven additional gene carriers were identified as a direct result of these studies, a 2-fold multiplying effect. We conclude routine application of RET proto-oncogene testing should be included in all cases of apparent sporadic MTC.
authors.affiliation: Section of Endocrinology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: N
authors.initials: N
authors.lastname: Wohllk
authors.forename: G J
authors.initials: GJ
authors.lastname: Cote
authors.forename: M M
authors.initials: MM
authors.lastname: Bugalho
authors.forename: N
authors.initials: N
authors.lastname: Ordonez
authors.forename: D B
authors.initials: DB
authors.lastname: Evans
authors.forename: H
authors.initials: H
authors.lastname: Goepfert
authors.forename: S
authors.initials: S
authors.lastname: Khorana
authors.forename: P
authors.initials: P
authors.lastname: Schultz
authors.forename: C S
authors.initials: CS
authors.lastname: Richards
authors.forename: R F
authors.initials: RF
authors.lastname: Gagel
mesh_terms: D001483:Base Sequence; D018276:Carcinoma, Medullary / Q000235:genetics*; D003062:Codon; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000032:analysis; D029721:Drosophila Proteins; D005091:Exons; D006801:Humans; 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*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: D003062:Codon; D017931:DNA Primers; D004273:DNA, Neoplasm; 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