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

Nat Genet. 1994 Jan;6(1):70-4. doi: 10.1038/ng0194-70.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Carcinoma, Medullary / genetics*
  • DNA Mutational Analysis
  • DNA Primers / genetics
  • Drosophila Proteins*
  • Exons
  • Humans
  • Molecular Sequence Data
  • Multiple Endocrine Neoplasia / genetics*
  • Phenotype
  • Point Mutation
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-ret
  • Proto-Oncogenes*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Thyroid Neoplasms / genetics*

Substances

  • DNA Primers
  • Drosophila Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases
  • Ret protein, Drosophila