The gene for multiple endocrine neoplasia type 1: Recent findings

S. J. Marx, S. K. Agarwal, C. Heppner, Y. S. Kim, M. B. Kester, P. K. Goldsmith, M. C. Skarulis, Allen M. Spiegel, A. L. Burns, L. V. Debelenko, Z. Zhuang, I. A. Lubensky, L. A. Liotta, M. R. Emmert-Buck, S. C. Guru, P. Manickam, J. S. Crabtree, F. S. Collins, S. C. Chandrasekharappa

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is a promising model to understand endocrine and other tumors. Its most common endocrine expressions are tumors of parathyroids, entero-pancreatic neuro-endocrine tissue, and anterior pituitary. Recently, collagenomas and multiple angiofibromas of the dermis also have been recognized as very common. MEN1 can be characterized from different perspectives: (a) as a hormone (parathyroid hormone, gastrin, prolactin, etc.) excess syndrome with excellent therapeutic options; (b) as a syndrome with sometimes lethal outcomes from malignancy of entero-pancreatic neuro-endocrine or foregut carcinoid tissues; or (c) as a disorder than can give insight about cell regulation in the endocrine, the dermal, and perhaps other tissue systems. The MEN1 gene was identified recently by positional cloning, a comprehensive strategy of narrowing the candidate interval and evaluating all or most genes in that interval. This discovery has opened new approaches to basic and clinical issues. Germline MEN1 mutations have been identified in most MEN1 families. Germline MEN1 mutations were generally not found in families with isolated hyperparathyroidism or with isolated pituitary tumor. Thus, studies with the MEN1 gene helped establish that mutation of other gene(s) is likely causative of these two MEN1 phenocopies. MEN1 proved to be the gene most frequent L4 mutated in common-variety, nonhereditary parathyroid tumor, gastrinoma, insulinoma, or bronchial carcinoid. For example, in common-variety parathyroid tumors, mutation of several other genes (such as cyclin D1 and P53) has been found, but much less frequently than MEN1 mutation. The majority of germline and somatic MEN1 mutations predicted truncation of the encoded protein (menin). Such inactivating mutations strongly supported prior predictions that MEN1 is a tumor suppressor gene insofar as stepwise mutational inactivation of both copies can release a cell from normal growth suppression. Menin is principally a nuclear protein; menin interacts with junD. Future studies, such as discovery of menin's metabolic pathway, could lead to new opportunities in cell biology and in tumor therapy.

Original languageEnglish (US)
Pages (from-to)119-122
Number of pages4
JournalBone
Volume25
Issue number1
DOIs
StatePublished - Jul 1999
Externally publishedYes

Fingerprint

Multiple Endocrine Neoplasia Type 1
Genes
Mutation
Neoplasms
Carcinoid Tumor
Gastrinoma
Angiofibroma
Insulinoma
Hyperparathyroidism
Cyclin D1
Gastrins
Pituitary Neoplasms
Dermis
Nuclear Proteins
Metabolic Networks and Pathways
Tumor Suppressor Genes
Parathyroid Hormone
Prolactin
Cell Biology
Organism Cloning

Keywords

  • Gastrinoma
  • Hyperparathyroid
  • Mesenchyme
  • Mutation
  • Oncogene
  • Positional cloning
  • Tumor suppressor

ASJC Scopus subject areas

  • Physiology
  • Hematology

Cite this

Marx, S. J., Agarwal, S. K., Heppner, C., Kim, Y. S., Kester, M. B., Goldsmith, P. K., ... Chandrasekharappa, S. C. (1999). The gene for multiple endocrine neoplasia type 1: Recent findings. Bone, 25(1), 119-122. https://doi.org/10.1016/S8756-3282(99)00112-X

The gene for multiple endocrine neoplasia type 1 : Recent findings. / Marx, S. J.; Agarwal, S. K.; Heppner, C.; Kim, Y. S.; Kester, M. B.; Goldsmith, P. K.; Skarulis, M. C.; Spiegel, Allen M.; Burns, A. L.; Debelenko, L. V.; Zhuang, Z.; Lubensky, I. A.; Liotta, L. A.; Emmert-Buck, M. R.; Guru, S. C.; Manickam, P.; Crabtree, J. S.; Collins, F. S.; Chandrasekharappa, S. C.

In: Bone, Vol. 25, No. 1, 07.1999, p. 119-122.

Research output: Contribution to journalArticle

Marx, SJ, Agarwal, SK, Heppner, C, Kim, YS, Kester, MB, Goldsmith, PK, Skarulis, MC, Spiegel, AM, Burns, AL, Debelenko, LV, Zhuang, Z, Lubensky, IA, Liotta, LA, Emmert-Buck, MR, Guru, SC, Manickam, P, Crabtree, JS, Collins, FS & Chandrasekharappa, SC 1999, 'The gene for multiple endocrine neoplasia type 1: Recent findings', Bone, vol. 25, no. 1, pp. 119-122. https://doi.org/10.1016/S8756-3282(99)00112-X
Marx SJ, Agarwal SK, Heppner C, Kim YS, Kester MB, Goldsmith PK et al. The gene for multiple endocrine neoplasia type 1: Recent findings. Bone. 1999 Jul;25(1):119-122. https://doi.org/10.1016/S8756-3282(99)00112-X
Marx, S. J. ; Agarwal, S. K. ; Heppner, C. ; Kim, Y. S. ; Kester, M. B. ; Goldsmith, P. K. ; Skarulis, M. C. ; Spiegel, Allen M. ; Burns, A. L. ; Debelenko, L. V. ; Zhuang, Z. ; Lubensky, I. A. ; Liotta, L. A. ; Emmert-Buck, M. R. ; Guru, S. C. ; Manickam, P. ; Crabtree, J. S. ; Collins, F. S. ; Chandrasekharappa, S. C. / The gene for multiple endocrine neoplasia type 1 : Recent findings. In: Bone. 1999 ; Vol. 25, No. 1. pp. 119-122.
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abstract = "Multiple endocrine neoplasia type 1 (MEN1) is a promising model to understand endocrine and other tumors. Its most common endocrine expressions are tumors of parathyroids, entero-pancreatic neuro-endocrine tissue, and anterior pituitary. Recently, collagenomas and multiple angiofibromas of the dermis also have been recognized as very common. MEN1 can be characterized from different perspectives: (a) as a hormone (parathyroid hormone, gastrin, prolactin, etc.) excess syndrome with excellent therapeutic options; (b) as a syndrome with sometimes lethal outcomes from malignancy of entero-pancreatic neuro-endocrine or foregut carcinoid tissues; or (c) as a disorder than can give insight about cell regulation in the endocrine, the dermal, and perhaps other tissue systems. The MEN1 gene was identified recently by positional cloning, a comprehensive strategy of narrowing the candidate interval and evaluating all or most genes in that interval. This discovery has opened new approaches to basic and clinical issues. Germline MEN1 mutations have been identified in most MEN1 families. Germline MEN1 mutations were generally not found in families with isolated hyperparathyroidism or with isolated pituitary tumor. Thus, studies with the MEN1 gene helped establish that mutation of other gene(s) is likely causative of these two MEN1 phenocopies. MEN1 proved to be the gene most frequent L4 mutated in common-variety, nonhereditary parathyroid tumor, gastrinoma, insulinoma, or bronchial carcinoid. For example, in common-variety parathyroid tumors, mutation of several other genes (such as cyclin D1 and P53) has been found, but much less frequently than MEN1 mutation. The majority of germline and somatic MEN1 mutations predicted truncation of the encoded protein (menin). Such inactivating mutations strongly supported prior predictions that MEN1 is a tumor suppressor gene insofar as stepwise mutational inactivation of both copies can release a cell from normal growth suppression. Menin is principally a nuclear protein; menin interacts with junD. Future studies, such as discovery of menin's metabolic pathway, could lead to new opportunities in cell biology and in tumor therapy.",
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AU - Chandrasekharappa, S. C.

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