@article{00f753760cb34bc4a73d48d5321b3879,
title = "Mycand loss of p53 cooperate to drive formation of choroid plexus carcinoma",
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.",
author = "Jun Wang and Merino, {Diana M.} and Nicholas Light and Murphy, {Brian L.} and Wang, {Yong Dong} and Xiaohui Guo and Hodges, {Andrew P.} and Chau, {Lianne Q.} and Liu, {Kun Wei} and Girish Dhall and Shahab Asgharzadeh and Kiehna, {Erin N.} and Shirey, {Ryan J.} and Janda, {Kim D.} and Taylor, {Michael D.} and David Malkin and Ellison, {David W.} and VandenBerg, {Scott R.} and Eberhart, {Charles G.} and Sears, {Rosalie C.} and Rousse, {Martine F.} and Gilbertson, {Richard J.} and Wechsler-Reya, {Robert J.}",
note = "Funding Information: We thank Diane Chun, Tracy Ho, and Ngan Nham for assistance with mouse genotyping; Lili Lacarra and the SBP Animal Facility for assistance with colony maintenance; Jesus Olvera and Cody Fine of the Human Embryonic Stem Cell Core at UCSD, and Yoav Altman of the SBP Flow Cytometry Shared Resource for help with FACS sorting; Fu-Yue Zeng of the Conrad Prebys Center for Chemical Genomics at SBP for help with high-throughput screening, Subu Govindarajan of the SBP Analytical Genomics Shared Resource for help with microarray analysis; Feng Qi and Jian-Liang (Jason) Li of the SBP Bioinformatics Shared Resource for help with analysis of microarray data. We are grateful to Joanna Phillips and the UCSF Brain Tumor SPORE Tissue Core (P50CA097257) and to Jim Loukides and the SickKids Brain Tumour Research Center Biobank for providing patient samples, and to Peter Vogt from the Scripps Research Institute for assistance with the MYC inhibitor KJ-Pyr-9. This work was supported by funding from the NCI (P30 CA30199, R01 CA122759, and R01 CA159859 to R. J. Wechsler-Reya; R01 CA96832 and R01 CA21765 to M.F. Roussel), the American Lebanese-Syrian Associated Charities (to M.F. Roussel), a National Brain Tumor Society Developmental Neurobiology Grant (to R.J. Wechsler-Reya), and a Leadership Award from the California Institute for Regenerative Medicine (LA1-01747, to R.J. Wechsler-Reya).",
year = "2019",
doi = "10.1158/0008-5472.CAN-18-2565",
language = "English (US)",
volume = "79",
pages = "2208--2219",
journal = "Cancer Research",
issn = "0008-5472",
number = "9",
}