Nature Publishing Group, publisher of Nature, and other science journals and reference works
Nature
my account e-alerts subscribe register
   
Tuesday 23 May 2017
Journal Home
Current Issue
AOP
Archive
Download PDF
References
Export citation
Export references
Send to a friend
More articles like this

Letters to Nature
Nature 367, 375 - 376 (27 January 1994); doi:10.1038/367375a0

A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma

Robert M. W. Hofstra*, Rudy M. Landsvater, Isabella Ceccherini, Rein P. Stulp*, Tineke Stelwagen*, Yin Luo, Barbara Pasini, Jo W. M. Hoppener, Hans Kristian Ploos van Amstel, Giovanni Romeo, Cornells J. M. Lips & Charles H. C. M. Buys*§

*Department of Medical Genetics, University of Groningen, Ant. Deusinglaan 4, 9713 AW Groningen, The Netherlands
Department of Internal Medicine and Pathology, Utrecht University Hospital, Clinical Genetics Centre, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
Laboratorio di Genetica Molecolare, Institute G. Gaslini, 16148 Genova, Italy
§To whom correspondence should be addressed.

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.

------------------

References

1. Mulligan, L. M. et al. Nature 363, 458−460 (1993). | Article | PubMed | ISI | ChemPort |
2. Donis-Keller, H. et al. Hum. molec. Genet. 2, 851−856 (1993). | PubMed | ChemPort |
3. Jackson, C. E., Block, M. A., Greenawald, K. A. & Tashjian, A. H. Am. J. hum. Genet. 101, 704−710 (1979).
4. Mathew, C. G. P. et al. Nature 328, 527−528 (1987). | Article | PubMed | ISI | ChemPort |
5. Simpson, N. E. et al. Nature 328, 528−530 (1987). | Article | PubMed | ISI | ChemPort |
6. Norum, R. A. et al. Genomics 8, 313−317 (1990). | Article | PubMed | ISI | ChemPort |
7. Landsvater, R. M. et al. Genomics 4, 246−250 (1989). | Article | PubMed | ChemPort |
8. Nelkin, B. D. et al. Cancer Res. 49, 4114−4119 (1989). | PubMed | ISI | ChemPort |
9. Ceccherini, I. et al. Biochem. biophys. Res. Commun. 196, 1288−1295 (1993). | Article | PubMed | ChemPort |
10. Takahashi, M. et al. Oncogene 3, 571−578 (1988). | PubMed | ISI | ChemPort |
11. Hanks, S. K., Quinn, A. M. & Hunter, T. Science 241, 42−52 (1988). | PubMed | ISI | ChemPort |
12. Schneider, R. Trends biochem. Sci. 17, 468−469 (1992). | Article | PubMed | ChemPort |
13. Schuchardt, A., Agati, V. D., Costantini, G. & Pachnis, V. Abstr. Cold Spring Harbor Meeting on Mouse Molecular Genetics 1992.
14. Orita, M., Suzuki, Y., Sekiya, T. & Hayashi, K. Genomics 5, 873−879 (1989).



© 1994 Nature Publishing Group
Privacy Policy