- Title
- Generation and multi-dimensional profiling of a childhood cancer cell line atlas defines new therapeutic opportunities
- Creator
- Sun, Claire Xin; Daniel, Paul; Adjumain, Shazia; Sun, Christie; Chong, Wai Chin; Fernando, Dasun; Drinkwater, Caroline; Tourchi, Motahhareh; Habarakada, Dilru; Sooraj, Dhanya; Carvalho, Diana; Storm, Phillip B.; Bradshaw, Gabrielle; Baubet, Valerie; Sayles, LC; Fernandez, E; Nguyen, T; Pörksen, M; Doan, A; Crombie, DE; Panday, M; Zhukova, N; Dun, Matthew D.; Shi, Hui; Ludlow, LE; Day, B; Stringer, BW; Neeman, N; Rubens, JA; Raabe, EH; Vinci, M; Tyrrell, V; Fletcher, JI; Ekert, PG; Loi, Melissa; Dumevska, B; Ziegler, DS; Tsoli, M; Syed Sulaiman, NF; Loh, AHP; Low, SYY; Sweet-Cordero, EA; Monje, M; Resnick, A; Jones, C; Chew, Nicole; Downie, P; Williams, B; Rosenbluh, J; Gough, D; Cain, JE; Firestein, R; Parackal, Sarah; Tsui, Vanessa; Liang, Yuqing; Koptyra, Mateusz
- Relation
- Cancer Cell Vol. 41, Issue 4, p. 660-677.e7
- Publisher Link
- http://dx.doi.org/10.1016/j.ccell.2023.03.007
- Publisher
- Cell Press
- Resource Type
- journal article
- Date
- 2023
- Description
- 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.
- Subject
- multi-omics feature analysis; machine learning; targeted therapy; biomarker; CRISPR screens; cell line atlas; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1482490
- Identifier
- uon:50946
- Identifier
- ISSN:1535-6108
- Language
- eng
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