Format

Send to

Choose Destination
Cancer Res. 2019 Mar 18. pii: canres.2565.2018. doi: 10.1158/0008-5472.CAN-18-2565. [Epub ahead of print]

Myc and loss of p53 cooperate to drive formation of choroid plexus carcinoma.

Author information

1
Tumor Initiation and Maintenance, Sanford Burnham Prebys Medical Discovery Institute.
2
Science Policy, Friends of Cancer Research.
3
Program in Genetics and Genome Biology, Hospital for Sick Children.
4
Department of Tumor Cell Biology, St. Jude Children's Research Hospital.
5
Computational Biology, St. Jude Children's Research Hospital.
6
Bioinformatics Shared Resource, NCI-designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute.
7
Tumor Initiation and Maintenance Program, Sanford Burnham Prebys Medical Discovery Institute.
8
Pediatrics, Children's Hospital of Los Angeles.
9
Pediatrics, Division of Hematology, Oncology and Blood and Marrow Transplantation; Pathology and Lab Medicine, Children's Hospital Los Angeles and The Saban Research Institute, Keck School of Medicine of University of Southern California.
10
Division of Hematology, Oncology and Blood & Marrow Transplantation, Children's Center for Cancer and Blood Diseases, Children's Hospital of Los Angeles.
11
Department of Chemistry, Immunology and The Skaggs Institute for Chemical Biology, Scripps Research Institute.
12
Chemistry, Scripps Research Institute.
13
The Arthur and Sonia Labatt Brain Tumor Research Centre, Hospital for Sick Children.
14
Dept. of Paediatrics, Hospital for Sick Children.
15
Pathology, St. Jude Children's Research Hospital.
16
Pathology, University of California, San Diego.
17
Pathology,Oncology, Ophthalmology, Johns Hopkins University School of Medicine.
18
Molecular and Medical Genetics, Oregon Health and Science University.
19
Tumor Cell Biology, MS# 350, St. Jude Children's Research Hospital.
20
Oncology/CRUK Cambridge Institute, University of Cambridge.
21
Tumor Initiation and Maintenance Program, Sanford Burnham Prebys Medical Discovery Institute rwreya@SBPdiscovery.org.

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. 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 histological 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.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center