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

2023; Cell Press; Volume: 41; Issue: 4 Linguagem: Inglês

10.1016/j.ccell.2023.03.007

1878-3686

Claire Sun, Paul Daniel, Gabrielle Bradshaw, Hui Shi, Melissa Loi, Nicole J. Chew, Sarah Parackal, Vanessa Tsui, Yuqing Liang, Mateusz Koptyra, Shazia Adjumain, Christie Sun, Wai Chin Chong, Dasun Fernando, Caroline Drinkwater, Motahhareh Tourchi, Dilru Habarakada, Dhanya Sooraj, Diana Carvalho, Phillip B. Storm, Valérie Baubet, Leanne C. Sayles, Elisabet Fernandez, Thy Nguyen, Mia Pörksen, Anh Doan, Duncan E. Crombie, Monty Panday, Nataliya Zhukova, Matthew D. Dun, Louise E. Ludlow, Bryan W. Day, Brett W. Stringer, Naama Neeman, Jeffrey Rubens, Eric H. Raabe, Maria Vinci, Vanessa Tyrrell, Jamie I. Fletcher, Paul G. Ekert, Biljana Dumevska, David S. Ziegler, Maria Tsoli, Nur Farhana Syed Sulaiman, Amos Hong Pheng Loh, Sharon Y. Y. Low, E. Alejandro Sweet‐Cordero, Michelle Monje, Adam Resnick, Chris Jones, Peter Downie, Bryan Williams, Joseph Rosenbluh, Daniel J. Gough, Jason E. Cain, Ron Firestein,

Neuroblastoma Research and Treatments

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.