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

Sun, CX; Daniel, P; Bradshaw, G; Shi, H; Loi, M; Chew, N; Parackal, S; Tsui, V; Liang, Y; Koptyra, M; Adjumain, S; Sun, C; Chong, WC; Fernando, D; Drinkwater, C; Tourchi, M; Habarakada, D; Sooraj, D; Carvalho, D; Storm, PB; Baubet, V; Sayles, LC; Fernandez, E; Nguyen, T; Porksen, M; Doan, A; Crombie, DE; Panday, M; Zhukova, N; Dun, MD; Ludlow, LE; Day, B; Stringer, BW; Neeman, N; Rubens, JA; Raabe, EH; Vinci, M; Tyrrell, V; Fletcher, JI; Ekert, PG; Dumevska, B; Ziegler, DS; Tsoli, M; Syed Sulaiman, NF; Loh, AHP; Low, SYY; Sweet-Cordero, EA; Monje, M; Resnick, A; Jones, C; Downie, P; Williams, B; Rosenbluh, J; Gough, D; Cain, JE; Firestein, R

Author(s): Sun, CX; Daniel, P; Bradshaw, G; Shi, H; Loi, M; Chew, N; Parackal, S; Tsui, V; Liang, Y; Koptyra, M; Adjumain, S; Sun, C; Chong, WC; Fernando, D; Drinkwater, C; Tourchi, M; Habarakada, D; Sooraj, D; Carvalho, D; Storm, PB; Baubet, V; Sayles, LC; Fernandez, E; Nguyen, T; Porksen, M; Doan, A; Crombie, DE; Panday, M; Zhukova, N; Dun, MD; Ludlow, LE; Day, B; Stringer, BW; Neeman, N; Rubens, JA; Raabe, EH; Vinci, M; Tyrrell, V; Fletcher, JI; Ekert, PG; Dumevska, B; Ziegler, DS; Tsoli, M; Syed Sulaiman, NF; Loh, AHP; Low, SYY; Sweet-Cordero, EA; Monje, M; Resnick, A; Jones, C; Downie, P; Williams, B; Rosenbluh, J; Gough, D; Cain, JE; Firestein, R;
Details: Publication Year 2023-04-10,Volume 41,Issue #4,Page 660-677.e7
Journal Title: Cancer Cell
Publication Type: Research article
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.
Publisher: Cell Press
Keywords: Child; Humans; *Brain Neoplasms/pathology; Cell Line, Tumor; CRISPR screens; biomarker; brain cancer; cell line atlas; epigenetics; machine learning; multi-omics feature analysis; pediatric cancers; precision medicine; targeted therapy
Department(s): Laboratory Research
PubMed ID: 37001527
Publisher's Version: https://doi.org/10.1016/j.ccell.2023.03.007
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-07-11 06:23:36

Last Modified: 2023-07-11 06:25:37