A protocol to establish cell line models from rare pediatric solid tumors.

Pediatric cell line models are important for basic and translational research. However, their establishment has been hampered by low success rates and the lack of a unified approach. Here, we present a protocol to establish pediatric cancer cell lines from rare childhood tumors. We describe the requirements for successful establishment, including an optimized dissociation technique, and the appropriate media conditions necessary for several types of rare but lethal forms of childhood cancers. For complete details on the use and execution of this protocol, please refer to Sun et al.1.

Generation and multi-dimensional profiling of a childhood cancer cell line atlas defines new therapeutic opportunities.

Pediatric solid and central nervous system tumors are the leading cause of cancer-related death among children. Identifying new targeted therapies necessitates the use of pediatric cancer models that faithfully recapitulate the patient's disease. However, the generation and characterization of pediatric cancer models has significantly lagged behind adult cancers, underscoring the urgent need to develop pediatric-focused cell line resources. Herein, we establish a single-site collection of 261 cell lines, including 224 pediatric cell lines representing 18 distinct extracranial and brain childhood tumor types. We subjected 182 cell lines to multi-omics analyses (DNA sequencing, RNA sequencing, DNA methylation), and in parallel performed pharmacological and genetic CRISPR-Cas9 loss-of-function screens to identify pediatric-specific treatment opportunities and biomarkers. Our work provides insight into specific pathway vulnerabilities in molecularly defined pediatric tumor classes and uncovers biomarker-linked therapeutic opportunities of clinical relevance. Cell line data and resources are provided in an open access portal.