OP10 * ROLE OF C-MYC IN CHOROID PLEXUS TUMOURS

Abstract

INTRODUCTION: Choroid plexus tumours (CPT) are intracranial brain tumours, predominantly occurring in children. They are classified into three prognostically relevant histological categories - choroid plexus papillomas (CPP), atypical choroid plexus papillomas (ACPP) and choroid plexus carcinomas (CPC). c-Myc is a proto-oncogene deregulated in various malignancies, including paediatric brain tumours such as medulloblastoma and glioma. While modelling c-Myc-driven brain tumourigenesis in the mouse, we unexpectedly found a significant incidence of CPTs in transgenic mice overexpressing c-Myc in neural progenitor cells. Here, we set out to test the hypothesis that deregulation of c-Myc expression plays a role in human CPTs. METHOD: RosaMycIB12; Nestin Cre mice were generated and kept under tumour watch until symptomatic or termination of the experiment (20 months of age), when histological analysis was performed on their brains. 46 human CPT samples were obtained from the MRC UK Brain Archive Information Network (BRAIN UK) and tested for c-Myc overexpression and c-Myc amplification by immunohistochemistry (IHC) and fluorescence in-situ hybridisation (FISH) respectively. RESULTS: CPT incidence in transgenic mice was 44% (18/41): 66% (12/18) CPP and 33% (6/18) CPC. No other tumour types were detected in these mice. No tumours were detected in the control cohort. Results of the on-going characterisation of c-Myc expression in the human tumours will be presented. CONCLUSION: Overexpression of c-Myc in neural progenitor cells leads to CPTs development in a proportion of the compound mutant mice. Translational analysis of the role of c-Myc in human CPTs will determine the validity of this model in mimicking the human tumours.