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

Claire Xin Sun, Paul Daniel, Gabrielle Bradshaw, Hui Shi, Melissa Loi, Nicole 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. StormValerie 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 Day, Brett W. Stringer, Naama Neeman, Jeffrey A. 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 Yin Yee Low, E. Alejandro Sweet-Cordero, Michelle Monje, Adam Resnick, Chris Jones, Peter Downie, Bryan Williams, Joseph Rosenbluh, Daniel Gough, Jason E. Cain, Ron Firestein

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)660-677.e7
Number of pages25
JournalCANCER CELL
Volume41
Issue number4
Early online date30 Mar 2023
DOIs
Publication statusPublished - 10 Apr 2023
Externally publishedYes

Keywords

  • biomarker
  • brain cancer
  • cell line atlas
  • CRISPR screens
  • epigenetics
  • machine learning
  • multi-omics feature analysis
  • pediatric cancers
  • precision medicine
  • targeted therapy

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