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Myc and 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 CPC patients depend on a deeper understanding of the mechanisms underlying the disease. 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 CPCs resemble their human counterparts at a histological level, and like the hypodiploid subset of human CPCs, exhibit multiple whole-chromosome losses, particularly of chromosomes 8, 12 and 19. Analysis of murine and human CPC gene expression profiles and copy number changes reveals altered expression of genes involved in cell cycle, DNA damage response and cilium function. Finally, high throughput drug screening identifies small molecule inhibitors that decrease the viability of CPCs. These models will be valuable tools for understanding the biology of choroid plexus tumors and for testing novel approaches to therapy.

ORGANISM(S): Mus musculus

PROVIDER: GSE126408 | GEO | 2020/01/28

REPOSITORIES: GEO

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Cross-species genomics identifies postanatal CPE as novel choroid plexus carcinoma oncogenes.

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