Molecular pathology of the MEN1 gene.
Multiple endocrine neoplasia type 1 (MEN1), among all syndromes, causes tumors in the highest number of tissue types. Most of the tumors are hormone producing (e.g., parathyroid, enteropancreatic endocrine, anterior pituitary) but some are not (e.g., angiofibroma). MEN1 tumors are multiple for organ type, for regions of a discontinuous organ, and for subregions of a continuous organ. Cancer contributes to late mortality; there is no effective prevention or cure for MEN1 cancers. Morbidities are more frequent from benign than malignant tumor, and both are indicators for screening. Onset age is usually earlier in a tumor type of MEN1 than of nonhereditary cases. Broad trends contrast with those in nonneoplastic excess of hormones (e.g., persistent hyperinsulinemic hypoglycemia of infancy). Most germline or somatic mutations in the MEN1 gene predict truncation or absence of encoded menin. Similarly, 11q13 loss of heterozygosity in tumors predicts inactivation of the other MEN1 copy. MEN1 somatic mutation is prevalent in nonhereditary, MEN1-like tumor types. Compiled germline and somatic mutations show almost no genotype/phenotype relation. Normal menin is 67 kDa, widespread, and mainly nuclear. It may partner with junD, NF-kB, PEM, SMAD3, RPA2, FANCD2, NM23beta, nonmuscle myosin heavy chain II-A, GFAP, and/or vimentin. These partners have not clarified menin's pathways in normal or tumor tissues. Animal models have opened approaches to menin pathways. Local overexpression of menin in Drosophila reveals its interaction with the jun-kinase pathway. The Men1+/- mouse has robust MEN1; its most important difference from human MEN1 is marked hyperplasia of pancreatic islets, a tumor precursor stage.
Agarwal
Sunita K
SK
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Lee Burns
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Sukhodolets
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Kennedy
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Obungu
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Hickman
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Mullendore
Michael E
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Whitten
Ira
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Skarulis
Monica C
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Simonds
William F
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Mateo
Carmen
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Crabtree
Judy S
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Scacheri
Peter C
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Youngmi
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Novotny
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Garrett-Beal
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Libutti
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Richard Alexander
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Parisi
Michael J
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Oliver
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Chandrasekharappa
Settara C
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Collins
Francis S
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Spiegel
Allen M
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Marx
Stephen J
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D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009377:Multiple Endocrine Neoplasia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*
C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins