MODL-17. The Childhood Brain Cancer Cell Line Atlas: A Resource for Biomarker Identification and Therapeutic Development

Abstract

Abstract Cell lines represent the most versatile and widely used models of cancer and, as such, are critical for identifying and advancing new therapies. Strikingly, there is a significant gap in both the number of childhood brain cancer cell lines and their characterisation compared to their adult counterparts. To address this inequity, we established a childhood brain cancer cell line atlas (publicly available at vicpcc.org.au/dashboard) encompassing over 180 childhood CNS-derived cell lines, representing 20 tumour types and 11 molecular subtypes. Cell lines are characterized by whole genome, RNA-sequencing, phospho- and total proteomics, DNA methylation and ATAC-seq analyses. Multi-omic factor analysis revealed distinct lineage-specified classification of our cell line cohort. In parallel, high throughput drug and CRISPR/Cas9 screens were conducted to map the functional dependencies in over 70 childhood CNS cell lines, including 47 paediatric high grade glioma models. These screens identified both lineage and molecular-subtype specific genetic and drug dependencies, underscoring the utility of this wide-scale approach. Machine based learning approaches to predict genotype-phenotype correlations uncovered distinct paediatric-specific biomarkers of growth dependency, highlighting the unique genetic wiring underlying paediatric CNS tumours. Finally, by integrating functional, molecular and drug profiles of paediatric CNS cell lines, we construct a system to prioritize investigation of novel therapeutic target-biomarkers pairs in specific CNS tumour types.