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Specific mutations of the RET proto-oncogene are related to disease phenotype in MEN 2A and FMTC

Nature Genetics volume 6, pages 70–74 (1994)Cite this article

Abstract

We have analysed 118 families with inherited medullary thyroid carcinoma (MTC) for mutations of the RET proto–oncogene. These included cases of multiple endocrine neoplasia types 2A (MEN 2A) and 2B (MEN 2B) and familial MTC (FMTC). Mutations at one of 5 cysteines in the extracellular domain were found in 97% of patients with MEN 2A and 86% with FMTC but not in MEN 2B patients or normal controls. 84% of the MEN2A mutations affected codon 634. MEN 2A patients with a Cys634 to Arg substitution had a greater risk of developing parathyroid disease than those with other codon 634 mutations. Our data show a strong correlation between disease phenotype and the nature and position of the RET mutation, suggesting that a simple, constitutive activation of the RET tyrosine kinase is unlikely to explain the events leading to MEN 2A and FMTC.

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Author notes

  1. Lois M. Mulligan

    Present address: Department of Paediatrics, Queen's Universisty, Kingston, Ontario, K7L 3N6, Canada

Authors and Affiliations

  1. Cancer Research Campaign Human Cancer Genetics Research Group, Department of Pathology, University of Cambridge, Cambridge, CB2 1QP, UK

    Lois M. Mulligan, Charis Eng, Catherine S. Healey, John B.J. Kwok, Emily Gardner, Margaret A. Ponder & Bruce A.J. Ponder

  2. MRC Biostatistics Unit, Institute for Public Health, University of Cambridge, Cambridge, CB2 2SR, UK

    David Clayton

  3. Universitäts-Krankenhaus, Chirurgische Klinik, Universität Hamburg, 2000, Hamburg, 20, Germany

    Andrea Frilling

  4. Department of Medicine, Henry Ford Hospital, Detroit, Michigan, 48202–2689, USA

    Charles E. Jackson

  5. Medizinische Klinik und Poliklinik, Abteilung für innere Medizin-Endokrinologie, Johannes Gutenberg-Universität Mainz, Postfach 3960, 6500, Mainz, Germany

    Hendrik Lehnert

  6. Albert-Ludwigs-Universitat Freiburg, Abt Innere Medizin IV Nephrologie, D-79106, Freiburg, Germany

    Hartmut P.H. Neumann

  7. Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota, 55905, USA

    Stephen N. Thibodeau

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  1. Lois M. Mulligan
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  2. Charis Eng
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Mulligan, L., Eng, C., Healey, C. et al. Specific mutations of the RET proto-oncogene are related to disease phenotype in MEN 2A and FMTC. Nat Genet 6, 70–74 (1994). https://doi.org/10.1038/ng0194-70

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