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

Oncogene volume 18, pages 1369–1373 (1999)Cite this article

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.

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Acknowledgements

The authors thank K Hammje, M Sitte and I Schwarz for technical assistance. The Dana-Farber Cancer Institute Molecular Biology Core Facility is acknowledged for running the sequence gels. This study was supported by the Deutsche Forschungsgemeinschaft (to OG) and a Barr Investigatorship (to CE). CE is the Lawrence and Susan Marx Investigator in Human Cancer Genetics.

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Authors and Affiliations

  1. Human Cancer Genetics Program, Comprehensive Cancer Center, Ohio State University, 420 W. 12th Avenue, 690 MRF, Columbus, Ohio, 43210, USA

    Oliver Gimm, Debbie J Marsh, Patricia LM Dahia & Charis Eng

  2. Dana-Farber Cancer Institute, Harvard University, Boston, 02115, Massachusetts, USA

    Oliver Gimm, Donna S Neuberg, Debbie J Marsh, Patricia LM Dahia & Charis Eng

  3. Martin-Luther-Universität Halle-Wittenberg, Klinik für Allgemeinchirurgie, Ernst-Grube-Str. 40, 06097, Halle/Saale, Germany

    Cuong Hoang-Vu & Henning Dralle

  4. Endokrinologische Gemeinschaftspraxis, Brückenstraße 21, 69120, Heidelberg-Neuenheim, Germany

    Friedhelm Raue

  5. Martin-Luther-Universität Halle-Wittenberg, Institut für Pathologie, Magdeburger Str. 14, 06097, Halle/Saale, Germany

    Raoul Hinze

  6. Cancer Research Campaign Human Cancer Genetics Research Group, University of Cambridge, Cambridge, CB2 2QQ, UK

    Charis Eng

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Gimm, O., Neuberg, D., Marsh, D. et al. Over-representation of a germline RET sequence variant in patients with sporadic medullary thyroid carcinoma and somatic RET codon 918 mutation. Oncogene 18, 1369–1373 (1999). https://doi.org/10.1038/sj.onc.1202418

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