@article{6d51616628944e388616fda8c0317cff,
title = "Generation and multi-dimensional profiling of a childhood cancer cell line atlas defines new therapeutic opportunities",
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.",
keywords = "biomarker, brain cancer, cell line atlas, CRISPR screens, epigenetics, machine learning, multi-omics feature analysis, pediatric cancers, precision medicine, targeted therapy",
author = "Sun, {Claire Xin} and Paul Daniel and Gabrielle Bradshaw and Hui Shi and Melissa Loi and Nicole Chew and Sarah Parackal and Vanessa Tsui and Yuqing Liang and Mateusz Koptyra and Shazia Adjumain and Christie Sun and Chong, {Wai Chin} and Dasun Fernando and Caroline Drinkwater and Motahhareh Tourchi and Dilru Habarakada and Dhanya Sooraj and Diana Carvalho and Storm, {Phillip B.} and Valerie Baubet and Sayles, {Leanne C.} and Elisabet Fernandez and Thy Nguyen and Mia P{\"o}rksen and Anh Doan and Crombie, {Duncan E.} and Monty Panday and Nataliya Zhukova and Dun, {Matthew D.} and Ludlow, {Louise E.} and Bryan Day and Stringer, {Brett W.} and Naama Neeman and Rubens, {Jeffrey A.} and Raabe, {Eric H.} and Maria Vinci and Vanessa Tyrrell and Fletcher, {Jamie I.} and Ekert, {Paul G.} and Biljana Dumevska and Ziegler, {David S.} and Maria Tsoli and {Syed Sulaiman}, {Nur Farhana} and Loh, {Amos Hong Pheng} and Low, {Sharon Yin Yee} and Sweet-Cordero, {E. Alejandro} and Michelle Monje and Adam Resnick and Chris Jones and Peter Downie and Bryan Williams and Joseph Rosenbluh and Daniel Gough and Cain, {Jason E.} and Ron Firestein",
note = "Funding Information: We thank Monash Health and Royal Children{\textquoteright}s Hospital Pathology staff for assistance in tissue allocation, Dr. David Eisenstat for helpful discussion, Mr. Yuankun Zhu for data analysis, Ms. Steph Forman for editing assistance, and Mr. Ethan Newnham for annotation of BBB penetration. Funding for this project was generously provided by the Children{\textquoteright}s Cancer Foundation, Australia , Robert Connor Dawes Foundation , and the Medical Research Future Fund ( NHMRC Project 2007620 ). We thank over 30 contributing sites for providing cell lines and/or tissues from which cell lines were generated. A full list of cell line contributors is provided in the supplemental information . Funding Information: We thank Monash Health and Royal Children's Hospital Pathology staff for assistance in tissue allocation, Dr. David Eisenstat for helpful discussion, Mr. Yuankun Zhu for data analysis, Ms. Steph Forman for editing assistance, and Mr. Ethan Newnham for annotation of BBB penetration. Funding for this project was generously provided by the Children's Cancer Foundation, Australia, Robert Connor Dawes Foundation, and the Medical Research Future Fund (NHMRC Project 2007620). We thank over 30 contributing sites for providing cell lines and/or tissues from which cell lines were generated. A full list of cell line contributors is provided in the supplemental information. The studies were conceived and designed by R.F. J.E.C. D.G. J.A.R. B.W. and P. Downie. Cell line generation by R.F. C.J. A.R. M.M. E.A.S.-C. S.Y.Y.L. A.H.P.L. N.F.S.S. M. Torchi, D.S.J. B. Day, P.G.E. J.I.F. M.V. E.H.R. J.A.R. B.W.S. B. Dumevska, L.E.L. M.D.D. D. Carvalho, A.D. E.F. L.C.S. V.B. P.B.S. D.E.C. D.S. M. Tsoli, V. Tyrrell, M.K. N.C. and P. Daniel. Biobanking/platform by N.N. M.Panday, N.Z. D.H. and C.D. Experiments performed by R.F. D.E.C. A.D. M.P{\"o}rksen, T.N. D.S. D.F. W.C.C. C.S. S.A. S.P. H.S. Y.Q. V.Tsui, N.C. M.L. G.B. and P. Daniel. Computational analyses performed by R.F. P. Daniel, and C.X.S. Writing, manuscript preparation by R.F. P. Daniel, and C.X.S. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. Publisher Copyright: {\textcopyright} 2023 Elsevier Inc.",
year = "2023",
month = apr,
day = "10",
doi = "10.1016/j.ccell.2023.03.007",
language = "English",
volume = "41",
pages = "660--677.e7",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "4",
}
