BIOL-03. NOVEL GENETICALLY ENGINEERED MOUSE MODEL FOR CHOROID PLEXUS CARCINOMA MIMICS HUMAN DISEASE

Choroid plexus carcinomas (CPCs) are rare, aggressive malignant tumours of the central nervous system occurring mainly in children under the age of one. While advances in clinical and molecular stratification have enabled risk-adapted treatment planning and improvements in outcome for many types of childhood brain tumours, there has not been equivalent progress for children with CPC. This has largely been due to the low incidence, leading treatment strategies to be mostly based on case series and a “standard of care” has yet to be established. In order to elucidate a coordinated therapeutic strategy for children with CPC, it is imperative to develop in vitro and in vivo models to improve our understanding of the mechanisms underlying tumorigenesis. We hypothesised that we could develop a genetically engineered mouse model (GEMM) to recapitulate patient CPCs, allowing for an early age of onset and high penetrance rate for accurate and efficient preclinical studies. To develop this GEMM of CPC, we utilized Cre-Lox technology to target CPC cells of origin. We crossed mice that conditionally expressed Tp53 (flx/flx); Rb (flx/flx); Pten (flx/flx) with mice harbouring a Tg((Ttr-cre/Esr1*)1Vco) allele, as it drives selective Cre-recombination in the early embryonic choroid plexus. Using this methodology, we have managed to produce CPCs within 90 days and with a 95% penetrance rate which we characterised using our laboratory’s tumour characterisation pipeline comprising histological evaluation, transcriptome analysis and imaging. We then used this model to investigate the transformation of the choroid during tumorigenesis and test novel therapeutic approaches to improve outcomes for patients affected by CPC. Not only are we looking for a “standard of care” that is currently inexistent for CPC, but we are also looking for one that will have minimal side effects and, therefore, not jeopardise the future of these children.