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

Autor: Paul Daniel, Claire Sun, Mateusz Koptyra, Caroline Drinkwater, Nicole Chew, Gabrielle Bradshaw, Melissa Loi, Claire Shi, Motahhareh Tourchi, Sarah Parackal, Wai Chin Chong, Dasun Fernando, Shazia Adjumain, Hoang Nguyen, Dilru Habarakada, Dhanya Sooraj, Duncan Crombie, Nataliya Zhukova, Chris Jones, Jeffrey Rubens, Eric Raabe, Maria Vinci, Matt Dun, Louise Ludlow, Javad Nazarian, Jamie Fletcher, Paul Ekert, David Ziegler, Amos Hong Pheng Loh, Sharon Yin Yee Low, Michelle Monje, Naama Neeman, Bryan Williams, Adam Resnick, Daniel Gough, Jason Cain, Ron Firestein
Rok vydání: 2022
Předmět:
Zdroj: Neuro-Oncology. 24:i172-i172
ISSN: 1523-5866
1522-8517
Popis: 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.
Databáze: OpenAIRE
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