Abstract
MULTIPLE endocrine neoplasia type 2A (MEN 2A) is a dominantly inherited cancer syndrome that affects tissues derived from neural ectoderm. It is characterized by medullary thyroid carcinoma (MTC) and phaeochromocytomal. The MEN2A gene has recently been localized by a combination of genetic and physical mapping techniques to a 480-kilobase region in chromosome 10qll.2 (refs 2,3). The DNA segment encompasses the RET proto-oncogene, a receptor tyrosine kinase gene expressed in MTC and phaeochromocytoma and at lower levels in normal human thyroid4. This suggested RET as a candidate for the MEN2A gene. We have identified missense mutations of the RET proto-oncogene in 20 of 23 apparently distinct MEN 2A families, but not in 23 normal controls. Further, 19 of these 20 mutations affect the same conserved cysteine residue at the boundary of the RET extracellular and transmembrane domains.
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
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Schimke, R. N. A. Rev. Med. 35, 25–31 (1984).
Gardner, E. et al. Hum. molec. Genet. 2, 241–246 (1993).
Mole, S. E. Mulligan, L. M., Healey, S. C., Ponder, B. A. J. & Tunnacliffe, A. Hum. molec. Genet 2, 247–252 (1993).
Santoro, M. et. al. Oncogene 5, 1595–1598 (1990).
Ishizaka, T. et. al. Oncogene 4, 1519–1521 (1989).
Takahashi, M. et. al. Oncogene 3, 571–578 (1988).
Takahashi, M., Buma, Y. Hiai, H. Oncogene 4, 805–806 (1989).
Cotton, R. G. Rodrigues, N. R. & Campbell, R. D. Proc. natn. Acad. Sci. U.S.A. 85, 4397–4401 (1988).
Rodrigues, N. R. et. al. Proc. natn. Acad. Sci. U.S.A. 87, 7555–7559 (1990).
Iwamoto, T. et. al. Oncogene 8, 1087–1091 (1993).
Mulligan, L. M., Gardner, E., Papi L. & Ponder, B. A. J. Nucleic Acids Res. 19, 5795 (1991).
Yamamoto, M. et. al. Jap. J. clin. Oncol. 21, 149–152 (1991).
Tahira, T. et. al. Nucleic Acids Res. 18, 7472 (1991).
Fusco, A. et. al. Nature 328, 170–172 (1987).
Mulligan, L. M., Gardner, E., Smith, B. A., Mathew, C. G. P. & Ponder B. A. J. Genes Chrom. Cancer 6, 166–177 (1993).
Landsvater, R. M. et. al. Genomics 4, 246–250 (1989).
Nelkin, B. D. et. al. Cancer Res. 49, 4114–4119 (1989).
Roussel, M. F., Downing, J. R., Rettenmier, C. W. & Sherr, C. J. Cell. 55, 979–988 (1988).
Coulien, F. C. et. al. Molec. cell. Biol. 10, 4202–4210 (1990).
Bargmann, C. I., Hung, C. & Weinberg, R. A. Cell 45, 649–657 (1986).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mulligan, L., Kwok, J., Healey, C. et al. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature 363, 458–460 (1993). https://doi.org/10.1038/363458a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/363458a0
This article is cited by
-
Oncogenic alterations in advanced NSCLC: a molecular super-highway
Biomarker Research (2024)
-
Looking for RET alterations in thyroid cancer: clinical relevance, methodology and timing
Endocrine (2023)
-
Clinical Characteristics and Responses to Immune Checkpoint Inhibitors in RET-Aberrant Digestive Tract Tumours
Targeted Oncology (2023)
-
Controversy on the management of patients carrying RET p.V804M mutation
Endocrine (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)
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.