Relevance of RET proto-oncogene mutations in sporadic medullary thyroid carcinoma.
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.
Wohllk
N
N
Section of Endocrinology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Cote
G J
GJ
Bugalho
M M
MM
Ordonez
N
N
Evans
D B
DB
Goepfert
H
H
Khorana
S
S
Schultz
P
P
Richards
C S
CS
Gagel
R F
RF
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*
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