Mutations of the RET proto-oncogene in the multiple endocrine neoplasia type 2 syndromes, related sporadic tumours, and hirschsprung disease

Hum Mutat. 1997;9(2):97-109. doi: 10.1002/(SICI)1098-1004(1997)9:2<97::AID-HUMU1>3.0.CO;2-M.


The RET proto-oncogene codes for a receptor tyrosine kinase thought to play a role in the development of neural crest and its derivatives. Mutations in the RET proto-oncogene have been found in patients with the multiple endocrine neoplasia type 2 syndromes (MEN 2), the related sporadic tumours medullary thyroid carcinoma and pheochromocytoma, and familial and sporadic Hirschsprung disease, a syndrome of congenital absence of enteric innervation. Germline mutations in one of eight codons within RET cause the three subtypes of MEN 2, namely, MEN 2A, MEN 2B, and familial medullary thyroid carcinoma. Somatic mutation in an overlapping group of nine codons have been found in a proportion of sporadic medullary thyroid carcinoma and pheochromocytoma. In contrast to MEN 2, approximately 25% of patients with Hirschsprung disease have germline mutations scattered throughout the length of RET.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carcinoma, Medullary / genetics
  • Drosophila Proteins*
  • Endocrine Gland Neoplasms / genetics*
  • Genetic Testing
  • Germ-Line Mutation / genetics
  • Hirschsprung Disease / genetics*
  • Humans
  • Multiple Endocrine Neoplasia Type 2a / genetics*
  • Mutation*
  • Neuroendocrine Tumors / genetics
  • Parathyroid Neoplasms / genetics
  • Pheochromocytoma / genetics
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Thyroid Neoplasms / genetics


  • Drosophila Proteins
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases
  • Ret protein, Drosophila