title: Molecular pathology of the MEN1 gene.
abstract: 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.
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Sunita K
authors.initials: SK
authors.lastname: Agarwal
authors.forename: A
authors.initials: A
authors.lastname: Lee Burns
authors.forename: Karen E
authors.initials: KE
authors.lastname: Sukhodolets
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Kennedy
authors.forename: Victor H
authors.initials: VH
authors.lastname: Obungu
authors.forename: Alison B
authors.initials: AB
authors.lastname: Hickman
authors.forename: Michael E
authors.initials: ME
authors.lastname: Mullendore
authors.forename: Ira
authors.initials: I
authors.lastname: Whitten
authors.forename: Monica C
authors.initials: MC
authors.lastname: Skarulis
authors.forename: William F
authors.initials: WF
authors.lastname: Simonds
authors.forename: Carmen
authors.initials: C
authors.lastname: Mateo
authors.forename: Judy S
authors.initials: JS
authors.lastname: Crabtree
authors.forename: Peter C
authors.initials: PC
authors.lastname: Scacheri
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Ji
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Novotny
authors.forename: Lisa
authors.initials: L
authors.lastname: Garrett-Beal
authors.forename: Jerrold M
authors.initials: JM
authors.lastname: Ward
authors.forename: Steven K
authors.initials: SK
authors.lastname: Libutti
authors.forename: H
authors.initials: H
authors.lastname: Richard Alexander
authors.forename: Aniello
authors.initials: A
authors.lastname: Cerrato
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Parisi
authors.forename: Sonia
authors.initials: S
authors.lastname: Santa Anna-A
authors.forename: Brian
authors.initials: B
authors.lastname: Oliver
authors.forename: Settara C
authors.initials: SC
authors.lastname: Chandrasekharappa
authors.forename: Francis S
authors.initials: FS
authors.lastname: Collins
authors.forename: Allen M
authors.initials: AM
authors.lastname: Spiegel
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Marx
mesh_terms: 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*
chemical_list: C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins