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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

920 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)375-376
Number of pages2
JournalNature
Volume367
Issue number6461
DOIs
Publication statusPublished - 1 Jan 1994

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