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

Lois M. Mulligan, Charis Eng, Catherine S. Healey, David Clayton, John B.J. Kwok, Emily Gardner, Margaret A. Ponder, Andrea Frilling, Charles E. Jackson, Hendrik Lehnert, Hartmut P.H. Neumann, Stephen N. Thibodeau, Bruce A.J. Ponder

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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.

Original languageEnglish (US)
Pages (from-to)70-74
Number of pages5
JournalNature Genetics
Volume6
Issue number1
DOIs
StatePublished - Jan 1994

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ASJC Scopus subject areas

  • Genetics

Cite this

Mulligan, L. M., Eng, C., Healey, C. S., Clayton, D., Kwok, J. B. J., Gardner, E., Ponder, M. A., Frilling, A., Jackson, C. E., Lehnert, H., Neumann, H. P. H., Thibodeau, S. N., & Ponder, B. A. J. (1994). Specific mutations of the RET proto-oncogene are related to disease phenotype in MEN 2A and FMTC. Nature Genetics, 6(1), 70-74. https://doi.org/10.1038/ng0194-70