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15 September 1998

Multiple Endocrine Neoplasia Type 1: Clinical and Genetic Topics

Authors: Stephen Marx, MD, Allen M. Spiegel, MD, Monica C. Skarulis, MD, John L. Doppman, MD, Francis S. Collins, MD, PhD, and Lance A. Liotta, MD, PhDAuthor, Article, & Disclosure Information
Publication: Annals of Internal Medicine
Volume 129, Number 6
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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.

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Information & Authors

Information

Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 129 • Number 6 • 15 September 1998
Pages: 484 - 494

History

Published in issue: 15 September 1998
Published online: 15 August 2000

Keywords

  1. Chromosomes
  2. DNA
  3. Endocrine tumors
  4. Germline mutation
  5. Heterozygosity
  6. Mutation
  7. Parathyroid
  8. Parathyroid tumors
  9. Proteins
  10. Tumor suppressor genes

Copyright

© 1998 American College of Physicians.

Authors

Affiliations

Stephen Marx, MD
Moderator (Marx)
Discussants (Spiegel, Skarulis, Doppman, Collins, Liotta)
For definitions of terms used, see Glossary at end of text.
An edited summary of a Clinical Staff Conference held on 4 June 1997 at the National Institutes of Health, Bethesda, Maryland.
Authors who wish to cite a section of the conference and specifically indicate its author may use this example for the form of the reference:
Skarulis MC. Clinical expressions of multiple endocrine neoplasia type 1 at the National Institutes of Health. pp 486-487. In: Marx S, moderator. Multiple endocrine neoplasia type 1: clinical and genetic topics. Ann Intern Med. 1998; 129:484-494.
View all articles by this author
Allen M. Spiegel, MD
Moderator (Marx)
Discussants (Spiegel, Skarulis, Doppman, Collins, Liotta)
For definitions of terms used, see Glossary at end of text.
An edited summary of a Clinical Staff Conference held on 4 June 1997 at the National Institutes of Health, Bethesda, Maryland.
Authors who wish to cite a section of the conference and specifically indicate its author may use this example for the form of the reference:
Skarulis MC. Clinical expressions of multiple endocrine neoplasia type 1 at the National Institutes of Health. pp 486-487. In: Marx S, moderator. Multiple endocrine neoplasia type 1: clinical and genetic topics. Ann Intern Med. 1998; 129:484-494.
View all articles by this author
Monica C. Skarulis, MD
Moderator (Marx)
Discussants (Spiegel, Skarulis, Doppman, Collins, Liotta)
For definitions of terms used, see Glossary at end of text.
An edited summary of a Clinical Staff Conference held on 4 June 1997 at the National Institutes of Health, Bethesda, Maryland.
Authors who wish to cite a section of the conference and specifically indicate its author may use this example for the form of the reference:
Skarulis MC. Clinical expressions of multiple endocrine neoplasia type 1 at the National Institutes of Health. pp 486-487. In: Marx S, moderator. Multiple endocrine neoplasia type 1: clinical and genetic topics. Ann Intern Med. 1998; 129:484-494.
View all articles by this author
John L. Doppman, MD
Moderator (Marx)
Discussants (Spiegel, Skarulis, Doppman, Collins, Liotta)
For definitions of terms used, see Glossary at end of text.
An edited summary of a Clinical Staff Conference held on 4 June 1997 at the National Institutes of Health, Bethesda, Maryland.
Authors who wish to cite a section of the conference and specifically indicate its author may use this example for the form of the reference:
Skarulis MC. Clinical expressions of multiple endocrine neoplasia type 1 at the National Institutes of Health. pp 486-487. In: Marx S, moderator. Multiple endocrine neoplasia type 1: clinical and genetic topics. Ann Intern Med. 1998; 129:484-494.
View all articles by this author
Francis S. Collins, MD, PhD
Moderator (Marx)
Discussants (Spiegel, Skarulis, Doppman, Collins, Liotta)
For definitions of terms used, see Glossary at end of text.
An edited summary of a Clinical Staff Conference held on 4 June 1997 at the National Institutes of Health, Bethesda, Maryland.
Authors who wish to cite a section of the conference and specifically indicate its author may use this example for the form of the reference:
Skarulis MC. Clinical expressions of multiple endocrine neoplasia type 1 at the National Institutes of Health. pp 486-487. In: Marx S, moderator. Multiple endocrine neoplasia type 1: clinical and genetic topics. Ann Intern Med. 1998; 129:484-494.
View all articles by this author
Lance A. Liotta, MD, PhD
Moderator (Marx)
Discussants (Spiegel, Skarulis, Doppman, Collins, Liotta)
For definitions of terms used, see Glossary at end of text.
An edited summary of a Clinical Staff Conference held on 4 June 1997 at the National Institutes of Health, Bethesda, Maryland.
Authors who wish to cite a section of the conference and specifically indicate its author may use this example for the form of the reference:
Skarulis MC. Clinical expressions of multiple endocrine neoplasia type 1 at the National Institutes of Health. pp 486-487. In: Marx S, moderator. Multiple endocrine neoplasia type 1: clinical and genetic topics. Ann Intern Med. 1998; 129:484-494.
View all articles by this author
Acknowledgments: The authors thank major collaborators, including Sunita K. Agarwal, Mary Beth Kester, Christina Heppner, Young S. Kim, Paul K. Goldsmith, and A. Lee Burns (all from the National Institute of Diabetes and Digestive and Kidney Disease [NIDDK]); Sirandanahalli C. Guru, Pachiappan Manickam, Shodimu-Emmanuel Olufemi, Judith Crabtree, and Settara C. Chandrasekharappa (all from the National Institute of Human Genome Research); Larissa V. Debelenko, Zhengping Zhuang, Irina A. Lubensky, and Michael R. Emmert-Buck (all from the National Cancer Institute); Mark Boguski and Jane Weisemann (both from the National Center for Biotechnology Information); Bruce Roe and Yingping Wang (both from the University of Oklahoma); and Jane S. Green (from Memorial University, Newfoundland, Canada). The authors also thank Lee S. Weinstein, William F. Simonds, and many current and former staff members and fellows in the NIDDK/National Institute of Child Health and Development Interinstitute Endocrine Fellowship Program and in the National Cancer Institute Surgery Branch.
Corresponding Author: Stephen J. Marx, MD, Building 10, Room 9C-101, National Institutes of Health, Bethesda, MD 20892.
Current Author Addresses: Dr. Marx: National Institutes of Health, Building 10, Room 9C-101, Bethesda, MD 20892.

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Stephen Marx, Allen M. Spiegel, Monica C. Skarulis, et al. Multiple Endocrine Neoplasia Type 1: Clinical and Genetic Topics. Ann Intern Med.1998;129:484-494. doi:10.7326/0003-4819-129-6-199809150-00011

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