TY - JOUR
T1 - Relevance of RET proto-oncogene mutations in sporadic medullary thyroid carcinoma
AU - Wohllk, Nelson
AU - Cote, Gilbert J.
AU - Bugalho, Maria M.J.
AU - Ordonez, Nelson
AU - Evans, Douglas B.
AU - Goepfert, Helmuth
AU - Khorana, Sangeeta
AU - Schultz, Pamela
AU - Richards, C. Sue
AU - Gagel, Robert F.
PY - 1996
Y1 - 1996
N2 - 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 (~25%) tumor DNA samples. Mutations were not identified in the remaining patients. In this large cancer center population, ~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.
AB - 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 (~25%) tumor DNA samples. Mutations were not identified in the remaining patients. In this large cancer center population, ~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.
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U2 - 10.1210/jc.81.10.3740
DO - 10.1210/jc.81.10.3740
M3 - Article
C2 - 8855832
AN - SCOPUS:10244245097
SN - 0021-972X
VL - 81
SP - 3740
EP - 3745
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 10
ER -