Mycand loss of p53 cooperate to drive formation of choroid plexus carcinoma

Jun Wang, Diana M. Merino, Nicholas Light, Brian L. Murphy, Yong Dong Wang, Xiaohui Guo, Andrew P. Hodges, Lianne Q. Chau, Kun Wei Liu, Girish Dhall, Shahab Asgharzadeh, Erin N. Kiehna, Ryan J. Shirey, Kim D. Janda, Michael D. Taylor, David Malkin, David W. Ellison, Scott R. VandenBerg, Charles G. Eberhart, Rosalie C. SearsMartine F. Rousse, Richard J. Gilbertson, Robert J. Wechsler-Reya

Research output: Contribution to journalArticle

2 Scopus citations

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 languageEnglish (US)
Pages (from-to)2208-2219
Number of pages12
JournalCancer Research
Volume79
Issue number9
DOIs
StatePublished - 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Wang, J., Merino, D. M., Light, N., Murphy, B. L., Wang, Y. D., Guo, X., Hodges, A. P., Chau, L. Q., Liu, K. W., Dhall, G., Asgharzadeh, S., Kiehna, E. N., Shirey, R. J., Janda, K. D., Taylor, M. D., Malkin, D., Ellison, D. W., VandenBerg, S. R., Eberhart, C. G., ... Wechsler-Reya, R. J. (2019). Mycand loss of p53 cooperate to drive formation of choroid plexus carcinoma. Cancer Research, 79(9), 2208-2219. https://doi.org/10.1158/0008-5472.CAN-18-2565