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Concomitant deletions of tumor suppressor genes MEN1 and AIP are essential for the pathogenesis of the brown fat tumor hibernoma.

Hansén Nord, Karolin LU ; Magnusson, Linda LU ; Isaksson, Margareth LU ; Nilsson, Jenny LU ; Lilljebjörn, Henrik LU orcid ; Domanski, Henryk LU ; Kindblom, Lars-Gunnar ; Mandahl, Nils LU and Mertens, Fredrik LU (2010) In Proceedings of the National Academy of Sciences Dec. p.21122-21127
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... (More)
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. (Less)
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published
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Proceedings of the National Academy of Sciences
volume
Dec
pages
21122 - 21127
publisher
National Academy of Sciences
external identifiers
  • wos:000285050800051
  • pmid:21078971
  • scopus:78650489189
  • pmid:21078971
ISSN
1091-6490
DOI
10.1073/pnas.1013512107
language
English
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yes
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The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Division of Clinical Genetics (013022003), Pathology, (Lund) (013030000)
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3fd1de9c-2e0f-439c-85af-78fee2f98344 (old id 1731942)
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http://f1000.com/6715956
http://www.ncbi.nlm.nih.gov/pubmed/21078971?dopt=Abstract
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2022-04-15 19:31:08
@article{3fd1de9c-2e0f-439c-85af-78fee2f98344,
  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.}},
  author       = {{Hansén Nord, Karolin and Magnusson, Linda and Isaksson, Margareth and Nilsson, Jenny and Lilljebjörn, Henrik and Domanski, Henryk and Kindblom, Lars-Gunnar and Mandahl, Nils and Mertens, Fredrik}},
  issn         = {{1091-6490}},
  language     = {{eng}},
  pages        = {{21122--21127}},
  publisher    = {{National Academy of Sciences}},
  series       = {{Proceedings of the National Academy of Sciences}},
  title        = {{Concomitant deletions of tumor suppressor genes MEN1 and AIP are essential for the pathogenesis of the brown fat tumor hibernoma.}},
  url          = {{http://dx.doi.org/10.1073/pnas.1013512107}},
  doi          = {{10.1073/pnas.1013512107}},
  volume       = {{Dec}},
  year         = {{2010}},
}