Relevance of RET proto-oncogene mutations in sporadic medullary thyroid carcinoma. J Clin Endocrinol Metab 1996 Oct;81(10):3740-5
Date
10/01/1996Pubmed ID
8855832DOI
10.1210/jcem.81.10.8855832Scopus ID
2-s2.0-10244245097 (requires institutional sign-in at Scopus site) 186 CitationsAbstract
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.
Author List
Wohllk N, Cote GJ, Bugalho MM, Ordonez N, Evans DB, Goepfert H, Khorana S, Schultz P, Richards CS, Gagel RFAuthor
Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Base SequenceCarcinoma, Medullary
Codon
DNA Primers
DNA, Neoplasm
Drosophila Proteins
Exons
Humans
Multiple Endocrine Neoplasia Type 2a
Mutation
Pedigree
Polymerase Chain Reaction
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-ret
Receptor Protein-Tyrosine Kinases
Thyroid Neoplasms
