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Article
Single Missense Mutation in the Tyrosine Kinase Catalytic Domain of the RET Protooncogene is Associated with Multiple Endocrine Neoplasia Type 2B.
1990-1999
  • Katrin M. Carlson, Division of Human Molecular Genetics
  • Shenshen Dou, Division of Human Molecular Genetics
  • David Chi, Division of Human Molecular Genetics
  • N. Scavarda, Washington University School of Medicine, MO
  • Koi Toshima, Nippon Medical School Tokyo, Japan
  • C. E. Jackson, Washington University School of Medicine, MO
  • Samuel A. Wells, Washington University School of Medicine, MO
  • Paul Goodfellow, Division of Human Molecular Genetics
  • Helen Donis-Keller, Franklin W. Olin College of Engineering
Document Type
Article
Publication Date
2-1-1994
Disciplines
Abstract
Multiple endocrine neoplasia type 2B (MEN 2B) is a human cancer syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytomas, mucosal neuromas, ganglioneuromas of the intestinal tract, and skeletal and ophthalmic abnormalities. It appears both as an inherited disorder and as de novo disease. Sequence analysis of germ-line DNA from MEN 2B patients revealed the existence of the same point mutation in the RET protooncogene in 34 unrelated individuals. This sequence difference was not observed in 93 unaffected individuals, including the normal parents of 14 de novo MEN 2B patients. The mutation (ATG-->ACG) results in the replacement of methionine with threonine within the catalytic core region of the tyrosine kinase domain. We propose that this amino acid replacement effects substrate interactions and results in dominant oncogenic activity by the RET protein. Missense mutations in the extracellular ligand-binding domain of the RET protooncogene previously have been associated with two other disorders [MEN 2A and familial MTC (FMTC)] in which MTC is observed. MEN 2B represents the third form of heritable MTC known to be an allele of RET. Alterations in two different functional domains of the putative receptor protein tyrosine kinase are implicated in development of MTC.
Comments

© 1994 National Academy of Sciences. This article was published in Proceedings of the National Academy of Science, vol. 91, iss. 4, pages 1579-1583 and may be found here.

Citation Information
Katrin M. Carlson, Shenshen Dou, David Chi, N. Scavarda, et al.. "Single Missense Mutation in the Tyrosine Kinase Catalytic Domain of the RET Protooncogene is Associated with Multiple Endocrine Neoplasia Type 2B." (1994)
Available at: http://works.bepress.com/helen_donis-keller/36/