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儿童癌症细胞系图谱的生成和多维分析定义新的治疗机会
2023-03-31 16:07

澳大利亚莫纳什大学Ron Firestein研究组发现,儿童癌症细胞系的生成和多维分析图谱定义新的治疗机会。2023年3月30日出版的《癌细胞》发表了这项成果。

他们建立了261个细胞系的单点收集,包括224个儿童细胞系,代表18种不同的颅外和脑肿瘤类型。他们对182个细胞系进行了多组学分析(DNA测序、RNA测序、DNA甲基化),并同时进行了药理和遗传CRISPR-Cas9功能丧失筛查,以确定儿科特异性治疗机会和生物标志物。他们的工作为分子定义的儿童肿瘤类别的特定通路脆弱性提供了见解,并揭示了临床相关性的生物标志物相关治疗机会。细胞系数据和资源可在一个开放访问门户中查看。

研究人员表示,小儿实体和中枢神经系统肿瘤是儿童癌症相关死亡的主要原因。确定新的靶向疗法需要使用忠实地概括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明显落后于成人癌症,这强调了开发以儿科为重点的细胞系资源的迫切需要。

附:英文原文

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

Author: 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 Prksen, 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

Issue&Volume: 2023-03-30

Abstract: Pediatric solid and central nervous system tumors are the leading cause of cancer-relateddeath among children. Identifying new targeted therapies necessitates the use of pediatriccancer models that faithfully recapitulate the patient’s disease. However, the generationand characterization of pediatric cancer models has significantly lagged behind adultcancers, underscoring the urgent need to develop pediatric-focused cell line resources.Herein, we establish a single-site collection of 261 cell lines, including 224 pediatriccell 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-Cas9loss-of-function screens to identify pediatric-specific treatment opportunities andbiomarkers. Our work provides insight into specific pathway vulnerabilities in molecularlydefined pediatric tumor classes and uncovers biomarker-linked therapeutic opportunitiesof clinical relevance. Cell line data and resources are provided in an open accessportal.

DOI: 10.1016/j.ccell.2023.03.007

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00080-6

Cancer Cell:《癌细胞》,创刊于2002年。隶属于细胞出版社,最新IF:38.585
官方网址:https://www.cell.com/cancer-cell/home
投稿链接:https://www.editorialmanager.com/cancer-cell/default.aspx


本期文章:《癌细胞》:Online/在线发表

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