Abstract
Choroid plexus carcinoma (CPC) is a rare brain tumor that occurs most commonly in very young children and has a dismal prognosis despite intensive therapy. Improved outcomes for patients with CPC depend on a deeper understanding of the mechanisms underlying the disease. Here we developed transgenic models of CPCs by activating the Myc oncogene and deleting the Trp53 tumor suppressor gene in murine neural stem cells or progenitors. Murine CPC resembled their human counterparts at a histologic level, and like the hypodiploid subset of human CPC, exhibited multiple wholechromosome losses, particularly of chromosomes 8, 12, and 19. Analysis of murine and human CPC gene expression profiles and copy number changes revealed altered expression of genes involved in cell cycle, DNA damage response, and cilium function. High-throughput drug screening identified small molecule inhibitors that decreased the viability of CPC. These models will be valuable tools for understanding the biology of choroid plexus tumors and for testing novel approaches to therapy. Significance: This study describes new mouse models of choroid plexus carcinoma and uses them to investigate the biology and therapeutic responsiveness of this highly malignant pediatric brain tumor.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2208-2219 |
| Number of pages | 12 |
| Journal | Cancer Research |
| Volume | 79 |
| Issue number | 9 |
| DOIs | |
| State | Published - Jan 1 2019 |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Mycand loss of p53 cooperate to drive formation of choroid plexus carcinoma. / Wang, Jun; Merino, Diana M.; Light, Nicholas; Murphy, Brian L.; Wang, Yong Dong; Guo, Xiaohui; Hodges, Andrew P.; Chau, Lianne Q.; Liu, Kun Wei; Dhall, Girish; Asgharzadeh, Shahab; Kiehna, Erin N.; Shirey, Ryan J.; Janda, Kim D.; Taylor, Michael D.; Malkin, David; Ellison, David W.; VandenBerg, Scott R.; Eberhart, Charles G.; Sears, Rosalie; Rousse, Martine F.; Gilbertson, Richard J.; Wechsler-Reya, Robert J.
In: Cancer Research, Vol. 79, No. 9, 01.01.2019, p. 2208-2219.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mycand loss of p53 cooperate to drive formation of choroid plexus carcinoma
AU - Wang, Jun
AU - Merino, Diana M.
AU - Light, Nicholas
AU - Murphy, Brian L.
AU - Wang, Yong Dong
AU - Guo, Xiaohui
AU - Hodges, Andrew P.
AU - Chau, Lianne Q.
AU - Liu, Kun Wei
AU - Dhall, Girish
AU - Asgharzadeh, Shahab
AU - Kiehna, Erin N.
AU - Shirey, Ryan J.
AU - Janda, Kim D.
AU - Taylor, Michael D.
AU - Malkin, David
AU - Ellison, David W.
AU - VandenBerg, Scott R.
AU - Eberhart, Charles G.
AU - Sears, Rosalie
AU - Rousse, Martine F.
AU - Gilbertson, Richard J.
AU - Wechsler-Reya, Robert J.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Choroid plexus carcinoma (CPC) is a rare brain tumor that occurs most commonly in very young children and has a dismal prognosis despite intensive therapy. Improved outcomes for patients with CPC depend on a deeper understanding of the mechanisms underlying the disease. Here we developed transgenic models of CPCs by activating the Myc oncogene and deleting the Trp53 tumor suppressor gene in murine neural stem cells or progenitors. Murine CPC resembled their human counterparts at a histologic level, and like the hypodiploid subset of human CPC, exhibited multiple wholechromosome losses, particularly of chromosomes 8, 12, and 19. Analysis of murine and human CPC gene expression profiles and copy number changes revealed altered expression of genes involved in cell cycle, DNA damage response, and cilium function. High-throughput drug screening identified small molecule inhibitors that decreased the viability of CPC. These models will be valuable tools for understanding the biology of choroid plexus tumors and for testing novel approaches to therapy. Significance: This study describes new mouse models of choroid plexus carcinoma and uses them to investigate the biology and therapeutic responsiveness of this highly malignant pediatric brain tumor.
AB - Choroid plexus carcinoma (CPC) is a rare brain tumor that occurs most commonly in very young children and has a dismal prognosis despite intensive therapy. Improved outcomes for patients with CPC depend on a deeper understanding of the mechanisms underlying the disease. Here we developed transgenic models of CPCs by activating the Myc oncogene and deleting the Trp53 tumor suppressor gene in murine neural stem cells or progenitors. Murine CPC resembled their human counterparts at a histologic level, and like the hypodiploid subset of human CPC, exhibited multiple wholechromosome losses, particularly of chromosomes 8, 12, and 19. Analysis of murine and human CPC gene expression profiles and copy number changes revealed altered expression of genes involved in cell cycle, DNA damage response, and cilium function. High-throughput drug screening identified small molecule inhibitors that decreased the viability of CPC. These models will be valuable tools for understanding the biology of choroid plexus tumors and for testing novel approaches to therapy. Significance: This study describes new mouse models of choroid plexus carcinoma and uses them to investigate the biology and therapeutic responsiveness of this highly malignant pediatric brain tumor.
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UR - http://www.scopus.com/inward/citedby.url?scp=85065510163&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-18-2565
DO - 10.1158/0008-5472.CAN-18-2565
M3 - Article
VL - 79
SP - 2208
EP - 2219
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 9
ER -