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Definition of Genetic Events Directing the Development of Distinct Types of Brain Tumors from Postnatal Neural Stem/Progenitor Cells.

Hertwig, Falk; Meyer, Katharina; Braun, Sebastian LU ; Ek, Sara; Spang, Rainer; Pfenninger, Cosima; Artner, Isabella LU ; Prost, Gaelle LU ; Chen, Xinbin and Biegel, Jaclyn A, et al. (2012) In Cancer Research 72(13). p.3381-3392
Abstract
Although brain tumors are classified and treated based upon their histology, the molecular factors involved in the development of various tumor types remain unknown. In this study, we show that the type and order of genetic events directs the development of gliomas, central nervous system primitive neuroectodermal tumors, and atypical teratoid/rhabdoid-like tumors from postnatal mouse neural stem/progenitor cells (NSC/NPC). We found that the overexpression of specific genes led to the development of these three different brain tumors from NSC/NPCs, and manipulation of the order of genetic events was able to convert one established tumor type into another. In addition, loss of the nuclear chromatin-remodeling factor SMARCB1 in rhabdoid... (More)
Although brain tumors are classified and treated based upon their histology, the molecular factors involved in the development of various tumor types remain unknown. In this study, we show that the type and order of genetic events directs the development of gliomas, central nervous system primitive neuroectodermal tumors, and atypical teratoid/rhabdoid-like tumors from postnatal mouse neural stem/progenitor cells (NSC/NPC). We found that the overexpression of specific genes led to the development of these three different brain tumors from NSC/NPCs, and manipulation of the order of genetic events was able to convert one established tumor type into another. In addition, loss of the nuclear chromatin-remodeling factor SMARCB1 in rhabdoid tumors led to increased phosphorylation of eIF2α, a central cytoplasmic unfolded protein response (UPR) component, suggesting a role for the UPR in these tumors. Consistent with this, application of the proteasome inhibitor bortezomib led to an increase in apoptosis of human cells with reduced SMARCB1 levels. Taken together, our findings indicate that the order of genetic events determines the phenotypes of brain tumors derived from a common precursor cell pool, and suggest that the UPR may represent a therapeutic target in atypical teratoid/rhabdoid tumors. Cancer Res; 72(13); 3381-92. ©2012 AACR. (Less)
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Contribution to journal
publication status
published
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Cancer Research
volume
72
issue
13
pages
3381 - 3392
publisher
American Association for Cancer Research
external identifiers
  • WOS:000307350700027
  • PMID:22719073
  • Scopus:84863584862
ISSN
1538-7445
DOI
10.1158/0008-5472.CAN-11-3525
language
English
LU publication?
yes
id
625f8489-9746-4673-a4e0-c6c6309f8acf (old id 2859180)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22719073?dopt=Abstract
date added to LUP
2012-07-04 18:35:11
date last changed
2016-12-04 04:41:43
@misc{625f8489-9746-4673-a4e0-c6c6309f8acf,
  abstract     = {Although brain tumors are classified and treated based upon their histology, the molecular factors involved in the development of various tumor types remain unknown. In this study, we show that the type and order of genetic events directs the development of gliomas, central nervous system primitive neuroectodermal tumors, and atypical teratoid/rhabdoid-like tumors from postnatal mouse neural stem/progenitor cells (NSC/NPC). We found that the overexpression of specific genes led to the development of these three different brain tumors from NSC/NPCs, and manipulation of the order of genetic events was able to convert one established tumor type into another. In addition, loss of the nuclear chromatin-remodeling factor SMARCB1 in rhabdoid tumors led to increased phosphorylation of eIF2α, a central cytoplasmic unfolded protein response (UPR) component, suggesting a role for the UPR in these tumors. Consistent with this, application of the proteasome inhibitor bortezomib led to an increase in apoptosis of human cells with reduced SMARCB1 levels. Taken together, our findings indicate that the order of genetic events determines the phenotypes of brain tumors derived from a common precursor cell pool, and suggest that the UPR may represent a therapeutic target in atypical teratoid/rhabdoid tumors. Cancer Res; 72(13); 3381-92. ©2012 AACR.},
  author       = {Hertwig, Falk and Meyer, Katharina and Braun, Sebastian and Ek, Sara and Spang, Rainer and Pfenninger, Cosima and Artner, Isabella and Prost, Gaelle and Chen, Xinbin and Biegel, Jaclyn A and Judkins, Alexander R and Englund, Elisabet and Nuber, Ulrike},
  issn         = {1538-7445},
  language     = {eng},
  number       = {13},
  pages        = {3381--3392},
  publisher    = {ARRAY(0xb040248)},
  series       = {Cancer Research},
  title        = {Definition of Genetic Events Directing the Development of Distinct Types of Brain Tumors from Postnatal Neural Stem/Progenitor Cells.},
  url          = {http://dx.doi.org/10.1158/0008-5472.CAN-11-3525},
  volume       = {72},
  year         = {2012},
}