Abstract
MULTIPLE endocrine neoplasia type 2 (MEN 2) comprises three clinically distinct, dominantly inherited cancer syndromes. MEN 2A patients develop medullary thyroid carcinoma (MTC) and phaeochromocytoma. MEN 2B patients show in addition ganglioneuromas of the gastrointestinal tract and skeletal abnormalities. In familial MTC, only the thyroid is affected. Germ-line mutations of the RET proto-oncogene have recently been reported in association with MEN 2A and familial MTC1,2. All mutations occurred within codons specifying cysteine residues in the transition point between the RETprotein extracellular and transmem-brane domains. We now show that MEN 2B is also associated with mutation of the RET proto-oncogene. A mutation in codon 664, causing the substitution of a threonine for a methionine in the tyrosine kinase domain of the protein, was found in all nine unrelated MEN 2B patients studied. The same mutation was found in six out of 18 sporadic tumours.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Mulligan, L. M. et al. Nature 363, 458–460 (1993).
Donis-Keller, H. et al. Hum. molec. Genet. 2, 851–856 (1993).
Jackson, C. E., Block, M. A., Greenawald, K. A. & Tashjian, A. H. Am. J. hum. Genet. 101, 704–710 (1979).
Mathew, C. G. P. et al. Nature 328, 527–528 (1987).
Simpson, N. E. et al. Nature 328, 528–530 (1987).
Norum, R. A. et al. Genomics 8, 313–317 (1990).
Landsvater, R. M. et al. Genomics 4, 246–250 (1989).
Nelkin, B. D. et al. Cancer Res. 49, 4114–4119 (1989).
Ceccherini, I. et al. Biochem. biophys. Res. Commun. 196, 1288–1295 (1993).
Takahashi, M. et al. Oncogene 3, 571–578 (1988).
Hanks, S. K., Quinn, A. M. & Hunter, T. Science 241, 42–52 (1988).
Schneider, R. Trends biochem. Sci. 17, 468–469 (1992).
Schuchardt, A., Agati, V. D., Costantini, G. & Pachnis, V. Abstr. Cold Spring Harbor Meeting on Mouse Molecular Genetics 1992.
Orita, M., Suzuki, Y., Sekiya, T. & Hayashi, K. Genomics 5, 873–879 (1989).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hofstra, R., Landsvater, R., Ceccherini, I. et al. A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma. Nature 367, 375–376 (1994). https://doi.org/10.1038/367375a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/367375a0
This article is cited by
-
Clinical Characteristics and Responses to Immune Checkpoint Inhibitors in RET-Aberrant Digestive Tract Tumours
Targeted Oncology (2023)
-
Circulating miR-26b-5p and miR-451a as diagnostic biomarkers in medullary thyroid carcinoma patients
Journal of Endocrinological Investigation (2023)
-
An integrative pan cancer analysis of RET aberrations and their potential clinical implications
Scientific Reports (2022)
-
Temporal trends in referrals of RET gene carriers for neck surgery to a tertiary surgical center in the era of international management guidelines
Endocrine (2022)
-
Clinical significance and interrelations of PD-L1 expression, Ki-67 index, and molecular alterations in sporadic medullary thyroid carcinoma from a Chinese population
Virchows Archiv (2022)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.