Multiple endocrine neoplasia type 1: Clinical and genetic topics

Stephen Marx, Allen M. Spiegel, Monica C. Skarulis, John L. Doppman, Francis S. Collins, Lance A. Liotta

Research output: Contribution to journalArticle

268 Citations (Scopus)

Abstract

Multiple endocrine neoplasia type 1 (MEN1) consists of benign, and sometimes malignant, tumors (often multiple in a tissue) of the parathyroids, enteropancreatic neuroendocrine system, anterior pituitary, and other tissues. Skin angiofibromas and skin collagenomas are common. Typically, MEN1 tumors begin two decades earlier than sporadic tumors. Because of tumor multiplicity and the tendency for postoperative tumor recurrence, specialized methods have been developed for preoperative and intraoperative localization of many MEN1-associated tumors. The MEN1 gene was recently isolated by positional cloning. This strategy progressively narrows the size of the candidate MEN1 gene interval on the chromosome and then finds and tests many or, if needed, all genes within that interval. The MEN1 gene was finally identified because it was the one gene that contained mutations in most DNAs from a test panel of MEN1 cases. It has been suggested that MEN1, like many hereditary cancer syndromes, is caused by mutation in a tumor suppressor gene that contributes to neoplasia when both gene copies in a tumor precursor cell have been sequentially inactivated ('two-hit' oncogenesis mechanism). Germline MEN1 mutations were found in most families with MEN1 and in most cases of sporadic MEN1. In addition, the MEN1 gene was the gene most likely to show acquired mutation in several sporadic or nonhereditary tumors- parathyroid adenomas, gastrinomas, insulinomas, and bronchial carcinoids. Most germline or acquired MEN1 mutations predicted truncation (and thus likely inactivation) of the encoded protein, supporting expectations for the 'first hit' to a tumor suppressor gene. Testing for MEN1 germline mutation is possible in a research setting. Candidates for MEN1 mutation testing include patients with MEN1 or its phenocopies and first-degree relatives of persons with MEN1.

Original languageEnglish (US)
Pages (from-to)484-494
Number of pages11
JournalAnnals of Internal Medicine
Volume129
Issue number6
StatePublished - Sep 15 1998
Externally publishedYes

Fingerprint

Multiple Endocrine Neoplasia Type 1
Neoplasms
Mutation
Genes
Tumor Suppressor Genes
Hereditary Neoplastic Syndromes
Gastrinoma
Angiofibroma
Parathyroid Neoplasms
Skin
Neurosecretory Systems
Insulinoma
Germ-Line Mutation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Marx, S., Spiegel, A. M., Skarulis, M. C., Doppman, J. L., Collins, F. S., & Liotta, L. A. (1998). Multiple endocrine neoplasia type 1: Clinical and genetic topics. Annals of Internal Medicine, 129(6), 484-494.

Multiple endocrine neoplasia type 1 : Clinical and genetic topics. / Marx, Stephen; Spiegel, Allen M.; Skarulis, Monica C.; Doppman, John L.; Collins, Francis S.; Liotta, Lance A.

In: Annals of Internal Medicine, Vol. 129, No. 6, 15.09.1998, p. 484-494.

Research output: Contribution to journalArticle

Marx, S, Spiegel, AM, Skarulis, MC, Doppman, JL, Collins, FS & Liotta, LA 1998, 'Multiple endocrine neoplasia type 1: Clinical and genetic topics', Annals of Internal Medicine, vol. 129, no. 6, pp. 484-494.
Marx S, Spiegel AM, Skarulis MC, Doppman JL, Collins FS, Liotta LA. Multiple endocrine neoplasia type 1: Clinical and genetic topics. Annals of Internal Medicine. 1998 Sep 15;129(6):484-494.
Marx, Stephen ; Spiegel, Allen M. ; Skarulis, Monica C. ; Doppman, John L. ; Collins, Francis S. ; Liotta, Lance A. / Multiple endocrine neoplasia type 1 : Clinical and genetic topics. In: Annals of Internal Medicine. 1998 ; Vol. 129, No. 6. pp. 484-494.
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