Single nucleotide polymorphisms act as modifiers and correlate with the development of medullary and simultaneous medullary/papillary thyroid carcinomas in 2 large, non-related families with the RET V804M proto-oncogene mutation.

Journal Article (Journal Article)

BACKGROUND: Single nucleotide polymorphisms (SNPs) may function as modifiers of the RET proto-oncogene, resulting in the expression of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC). We present 2 non-related Italian-American families (Family 1, n = 107; Family 2, n = 31) with the RET V804M mutation. We have correlated the presence of specific SNPs and the rare RET V804M mutation to MTC, C-cell hyperplasia (CCH), and PTC. METHODS: Sequencing was performed on exons 10, 11, and 13-16 of the RET proto-oncogene. The presence of MTC, CCH, and PTC were correlated to specific SNPs. RESULTS: In both families, 3 SNPs in exon 11 (G691S), exon 13 (L769L), and exon 15 (S904S) were detected in 100% of patients with overt MTC. The SNP L769L was present in all patients including patients with PTC, MTC, and CCH. CONCLUSION: SNP analysis revealed a similar pattern between the 2 families. SNPs in exon 11 (G691S) and exon 15 (S904S) appear to influence the development of MTC. A SNP in exon 13 (L769L) may serve as a modifier in the development of simultaneous MTC and PTC, as well as presentation of MTC, in patients with the RET V804M mutation.

Full Text

Duke Authors

Cited Authors

  • Shifrin, AL; Ogilvie, JB; Stang, MT; Fay, AM; Kuo, Y-H; Matulewicz, T; Xenachis, CZ; Vernick, JJ

Published Date

  • December 2010

Published In

Volume / Issue

  • 148 / 6

Start / End Page

  • 1274 - 1280

PubMed ID

  • 21134561

Electronic International Standard Serial Number (EISSN)

  • 1532-7361

Digital Object Identifier (DOI)

  • 10.1016/j.surg.2010.09.004


  • eng

Conference Location

  • United States