title: Concomitant deletions of tumor suppressor genes MEN1 and AIP are essential for the pathogenesis of the brown fat tumor hibernoma.
abstract: Hibernomas are benign tumors with morphological features resembling brown fat. They consistently display cytogenetic rearrangements, typically translocations, involving chromosome band 11q13. Here we demonstrate that these aberrations are associated with concomitant deletions of AIP and MEN1, tumor suppressor genes that are located 3 Mb apart and that underlie the hereditary syndromes pituitary adenoma predisposition and multiple endocrine neoplasia type I. MEN1 and AIP displayed a low expression in hibernomas whereas the expression of genes up-regulated in brown fat--PPARA, PPARG, PPARGC1A, and UCP1--was high. Thus, loss of MEN1 and AIP is likely to be pathogenetically essential for hibernoma development. Simultaneous loss of two tumor suppressor genes has not previously been shown to result from a neoplasia-associated translocation. Furthermore, in contrast to the prevailing assumption that benign tumors harbor relatively few genetic aberrations, the present analyses demonstrate that a considerable number of chromosome breaks are involved in the pathogenesis of hibernoma.
authors.affiliation: Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, SE-221 85 Lund, Sweden.
authors.forename: Karolin H
authors.initials: KH
authors.lastname: Nord
authors.forename: Linda
authors.initials: L
authors.lastname: Magnusson
authors.forename: Margareth
authors.initials: M
authors.lastname: Isaksson
authors.forename: Jenny
authors.initials: J
authors.lastname: Nilsson
authors.forename: Henrik
authors.initials: H
authors.lastname: Lilljebjörn
authors.forename: Henryk A
authors.initials: HA
authors.lastname: Domanski
authors.forename: Lars-Gunnar
authors.initials: LG
authors.lastname: Kindblom
authors.forename: Nils
authors.initials: N
authors.lastname: Mandahl
authors.forename: Fredrik
authors.initials: F
authors.lastname: Mertens
mesh_terms: D002001:Adipose Tissue, Brown; D002869:Chromosome Aberrations; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008067:Lipoma / Q000209:etiology / Q000235:genetics*; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics; D015854:Up-Regulation
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D047492:Peroxisome Proliferator-Activated Receptors; C103265:aryl hydrocarbon receptor-interacting protein