American Association for Cancer Research
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00085472can182565-sup-207246_2_supp_5376136_pnpd07.png (3.35 MB)

Supplementary Fig 2 from Myc and Loss of p53 Cooperate to Drive Formation of Choroid Plexus Carcinoma

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posted on 2023-03-31, 03:02 authored by 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. Sears, Martine F. Roussel, Richard J. Gilbertson, Robert J. Wechsler-Reya

Figure S2 shows H&E staining on Atoh1-Cre CPC.

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UCSF Brain Tumor SPORE Tissue Core

NCI

California Institute for Regenerative Medicine

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ARTICLE 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 whole-chromosome 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. 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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