Over-representation of a germline RET sequence variant in patients with sporadic medullary thyroid carcinoma and somatic RET codon 918 mutation

Oliver Gimm, Donna S. Neuberg, Debbie J. Marsh, Patricia L.M. Dahia, Cuong Hoang-Vu, Friedhelm Raue, Raoul Hinze, Henning Dralle, Charis Eng

Research output: Contribution to journalArticle

116 Scopus citations

Abstract

The aetiology of sporadic medullary thyroid carcinoma is unknown. About 50% harbour a somatic mutation at codon 918 of RET (M918T). To investigate whether other RET sequence variants may be associated with or predispose to the development of sporadic medullary thyroid carcinoma, we analysed genomic DNA from the germline and corresponding tumour from 50 patients to identify RET sequence variants. In one patient, tumour DNA showed a novel somatic 12 bp in-frame deletion in exon 15. More interestingly, we found that the rare polymorphism at codon 836 (c.2439C > T; S836S) occurred at a significantly higher frequency than that in control individuals without sporadic medullary thyroid carcinoma (Fisher's exact test, P = 0.03). Further, among the nine evaluable cases with germline c.2439C/T, eight also had the somatic M918T mutation in MTC DNA which was more frequent than in patients with the more common c.2439C/C (89% vs 40%, respectively; Fisher's exact test, P = 0.01). These findings suggest that the rare sequence variant at codon 836 may somehow play a role in the genesis of sporadic medullary thyroid carcinoma.

Original languageEnglish (US)
Pages (from-to)1369-1373
Number of pages5
JournalOncogene
Volume18
Issue number6
DOIs
StatePublished - Feb 11 1999
Externally publishedYes

Keywords

  • Germline mutation
  • Medullary thyroid cancer
  • Polymorphism
  • Somatic mutation
  • Tyrosine kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'Over-representation of a germline RET sequence variant in patients with sporadic medullary thyroid carcinoma and somatic RET codon 918 mutation'. Together they form a unique fingerprint.

  • Cite this