Fessler Jacob, Ting Stephanie, Yi Hong, Haase Santiago, Chen Jingting, Gulec Saygin, Wang Yue, Smyers Nathan, Goble Kohen, Cannon Danielle, Mehta Aarav, Ford Christina, Brunk Elizabeth
Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA.
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA.
NAR Cancer. 2024 Aug 1;6(3):zcae035. doi: 10.1093/narcan/zcae035. eCollection 2024 Sep.
Recently, the cancer community has gained a heightened awareness of the roles of extrachromosomal DNA (ecDNA) in cancer proliferation, drug resistance and epigenetic remodeling. However, a hindrance to studying ecDNA is the lack of available cancer model systems that express ecDNA. Increasing our awareness of which model systems express ecDNA will advance our understanding of fundamental ecDNA biology and unlock a wealth of potential targeting strategies for ecDNA-driven cancers. To bridge this gap, we created CytoCellDB, a resource that provides karyotype annotations for cell lines within the Cancer Dependency Map (DepMap) and the Cancer Cell Line Encyclopedia (CCLE). We identify 139 cell lines that express ecDNA, a 200% increase from what is currently known. We expanded the total number of cancer cell lines with ecDNA annotations to 577, which is a 400% increase, covering 31% of cell lines in CCLE/DepMap. We experimentally validate several cell lines that we predict express ecDNA or homogeneous staining regions (HSRs). We demonstrate that CytoCellDB can be used to characterize aneuploidy alongside other molecular phenotypes, (gene essentialities, drug sensitivities, gene expression). We anticipate that CytoCellDB will advance cytogenomics research as well as provide insights into strategies for developing therapeutics that overcome ecDNA-driven drug resistance.
最近，癌症研究领域对染色体外DNA（ecDNA）在癌症增殖、耐药性和表观遗传重塑中的作用有了更高的认识。然而，研究ecDNA的一个障碍是缺乏表达ecDNA的可用癌症模型系统。提高我们对哪些模型系统表达ecDNA的认识，将推动我们对ecDNA基本生物学的理解，并为ecDNA驱动的癌症解锁大量潜在的靶向策略。为了弥补这一差距，我们创建了CytoCellDB，这是一个为癌症依赖图谱（DepMap）和癌症细胞系百科全书（CCLE）中的细胞系提供核型注释的资源。我们鉴定出139个表达ecDNA的细胞系，比目前已知的数量增加了200%。我们将带有ecDNA注释的癌细胞系总数扩大到577个，增加了400%，覆盖了CCLE/DepMap中31%的细胞系。我们通过实验验证了几个我们预测表达ecDNA或均匀染色区（HSRs）的细胞系。我们证明CytoCellDB可用于与其他分子表型（基因必需性、药物敏感性、基因表达）一起表征非整倍体。我们预计CytoCellDB将推动细胞基因组学研究，并为开发克服ecDNA驱动的耐药性的治疗策略提供见解。
