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Polymorphisms in Exon 13 and Intron 14 of the RET Protooncogene: Genetic Modifiers of Medullary Thyroid Carcinoma?

Polymorphisms in Exon 13 and Intron 14 of the RET Protooncogene: Genetic Modifiers of Medullary... AbstractContext: Single-nucleotide polymorphisms (SNPs) of the RET protooncogene (RET) could modify disease susceptibility and clinical phenotype in patients with sporadic or familial medullary thyroid carcinoma (FMTC).Objective/Design of the Study: Because frequencies of RET SNPs have not yet been evaluated in patients with elevated serum concentrations of calcitonin (hCt), a biochemical marker for medullary thyroid carcinoma (MTC), we studied RET SNPs in patients with FMTC (n = 22), patients with sporadic MTC (n = 45), and 71 subjects presenting with moderately elevated hCt concentrations (basal, >10 pg/ml; pentagastrin stimulated, > 50 < 100 pg/ml) in comparison with an age- and gender-matched control group (n = 79) with basal hCt concentrations in the normal range (<5 pg/ml).Methods: After DNA extraction from citrated whole blood, RET exons 10, 11, 13, 14, 15, and 16 and exon/intron boundaries were analyzed by PCR-based cycle sequencing for RET germ line mutations, exonic (G691S, L769L, S836S, S904S) and intronic (IVS13+158; NCBI rs2472737 = IVS14–24) SNPs.Results: In FMTC patients, the F791Y mutation was found to be associated (P = 0.001) with the L769L SNP. The exonic SNPs (G691S, L769L, S836S, and S904S) were not different among the four groups. The intron 14 SNP (IVS14–24), however, was more frequent in individuals with elevated hCt serum concentrations (P = 0.016) and patients with sporadic MTC (P < 0.001) when compared with the control group.Conclusions: These data suggest that the exon 13 (L769L) and the intron 14 (IVS14–24) SNPs could act as genetic modifiers in the development of some forms of hereditary and sporadic MTC, respectively. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Clinical Endocrinology and Metabolism Oxford University Press

Polymorphisms in Exon 13 and Intron 14 of the RET Protooncogene: Genetic Modifiers of Medullary Thyroid Carcinoma?

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References (34)

Publisher
Oxford University Press
Copyright
Copyright © 2005 by The Endocrine Society
ISSN
0021-972X
eISSN
1945-7197
DOI
10.1210/jc.2005-1278
pmid
16118333
Publisher site
See Article on Publisher Site

Abstract

AbstractContext: Single-nucleotide polymorphisms (SNPs) of the RET protooncogene (RET) could modify disease susceptibility and clinical phenotype in patients with sporadic or familial medullary thyroid carcinoma (FMTC).Objective/Design of the Study: Because frequencies of RET SNPs have not yet been evaluated in patients with elevated serum concentrations of calcitonin (hCt), a biochemical marker for medullary thyroid carcinoma (MTC), we studied RET SNPs in patients with FMTC (n = 22), patients with sporadic MTC (n = 45), and 71 subjects presenting with moderately elevated hCt concentrations (basal, >10 pg/ml; pentagastrin stimulated, > 50 < 100 pg/ml) in comparison with an age- and gender-matched control group (n = 79) with basal hCt concentrations in the normal range (<5 pg/ml).Methods: After DNA extraction from citrated whole blood, RET exons 10, 11, 13, 14, 15, and 16 and exon/intron boundaries were analyzed by PCR-based cycle sequencing for RET germ line mutations, exonic (G691S, L769L, S836S, S904S) and intronic (IVS13+158; NCBI rs2472737 = IVS14–24) SNPs.Results: In FMTC patients, the F791Y mutation was found to be associated (P = 0.001) with the L769L SNP. The exonic SNPs (G691S, L769L, S836S, and S904S) were not different among the four groups. The intron 14 SNP (IVS14–24), however, was more frequent in individuals with elevated hCt serum concentrations (P = 0.016) and patients with sporadic MTC (P < 0.001) when compared with the control group.Conclusions: These data suggest that the exon 13 (L769L) and the intron 14 (IVS14–24) SNPs could act as genetic modifiers in the development of some forms of hereditary and sporadic MTC, respectively.

Journal

Journal of Clinical Endocrinology and MetabolismOxford University Press

Published: Nov 1, 2005

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