Abstract Cell lines are among the most versatile and commonly used models in cancer research, playing a vital role in the discovery and development of new therapies. However, a notable disparity exists in the number and characterization of childhood brain cancer cell lines compared to those derived from adult cancers. To address this gap, we developed the Childhood Brain Cancer Cell Line Atlas, publicly accessible at vicpcc.org.au/dashboard. This comprehensive resource includes over 300 childhood CNS-derived cell lines, spanning 20 tumor types and 17 molecular subtypes. Each cell line has been extensively characterized using whole-genome sequencing, RNA sequencing, phospho- and total proteomics, and DNA methylation analyses. Multi-omic factor analysis revealed distinct lineage-specific classifications within the cell line cohort. Additionally, high-throughput drug screening and genome-scale CRISPR/Cas12 experiments have been conducted on more than 50 childhood CNS cell lines to identify functional dependencies. These efforts uncover genetic and drug dependencies specific to both lineage and molecular subtypes, demonstrating the power of this large-scale approach. Furthermore, machine learning analyses of genotype-phenotype correlations revealed pediatric-specific biomarkers of growth dependency, providing insights into the unique genetic architecture of pediatric CNS tumors.
Ron Firestein (Fri,) studied this question.