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Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A

Nature volume 363, pages 458–460 (1993)Cite this article

Abstract

MULTIPLE endocrine neoplasia type 2A (MEN 2A) is a dominantly inherited cancer syndrome that affects tissues derived from neural ectoderm. It is characterized by medullary thyroid carcinoma (MTC) and phaeochromocytomal. The MEN2A gene has recently been localized by a combination of genetic and physical mapping techniques to a 480-kilobase region in chromosome 10qll.2 (refs 2,3). The DNA segment encompasses the RET proto-oncogene, a receptor tyrosine kinase gene expressed in MTC and phaeochromocytoma and at lower levels in normal human thyroid4. This suggested RET as a candidate for the MEN2A gene. We have identified missense mutations of the RET proto-oncogene in 20 of 23 apparently distinct MEN 2A families, but not in 23 normal controls. Further, 19 of these 20 mutations affect the same conserved cysteine residue at the boundary of the RET extracellular and transmembrane domains.

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Author notes

  1. Donald R. Love

    Present address: School of Biological Sciences, University of Auckland, Auckland, New Zealand

  2. Sara E. Mole

    Present address: Department of Paediatrics, University College of Middlesex School of Medicine, University College London, London, UK

  3. Laura Papi

    Present address: Dip. Fisiopathologia Clinica, Sezione di Genetica Medica, Viale Pieraccini 6, Firenze, Italy

  4. Bruce A. J. Ponder: To whom correspondence should be addressed

Authors and Affiliations

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

    Lois M. Mulligan, John B. J. Kwok, Catherine S. Healey, Mark J. Elsdon, Charis Eng, Emily Gardner, Julie K. Moore, Margaret A. Ponder, Hakan Telenius, Alan Tunnacliffe & Bruce A. J. Ponder

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  14. Bruce A. J. Ponder
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Mulligan, L., Kwok, J., Healey, C. et al. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature 363, 458–460 (1993). https://doi.org/10.1038/363458a0

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