儿童癌症细胞系图谱的生成和多维度分析定义了新的治疗机会。
Generation and multi-dimensional profiling of a childhood cancer cell line atlas defines new therapeutic opportunities.
发表日期:2023 Mar 22
作者:
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 Storm, Valerie 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
来源:
BIOMEDICINE & PHARMACOTHERAPY
摘要:
儿童实体和中枢神经系统肿瘤是致儿童癌症相关死亡的主要原因。确定新的靶向治疗方法需要使用能忠实重现患者疾病的儿科癌症模型。然而,儿童癌症模型的生成和表征显著滞后于成人癌症,强调了需要开发儿童专注的细胞系资源的紧迫性。在此,我们建立了一个单一网站集合,包括261个细胞系,其中包括224个代表18种不同的颅外和脑部儿童肿瘤类型的儿科细胞系。我们对182个细胞系进行了多组学分析(DNA测序、RNA测序、DNA甲基化),并同时进行药物和基因CRISPR-Cas9功能失活筛选,以识别儿童特异性治疗机会和生物标志物。我们的工作提供了分子定义的儿科肿瘤类中特定通路易感性的见解,并揭示了与生物标志物相关的临床相关治疗机会。细胞系数据和资源在开放访问门户中提供。版权所有©2023 Elsevier Inc.。
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.Copyright © 2023 Elsevier Inc. All rights reserved.