Abstract 7348: CytoCellDB: A gold standard database for classification and analysis of extrachromosomal DNA in cancer

Abstract

Abstract Extrachromosomal DNA (ecDNA), or double minute chromosomes, are established cytogenetic markers for malignancy and genome instability. More recently, the cancer community has gained a heightened awareness of the roles of ecDNA in cancer proliferation, drug resistance and epigenetic remodeling. A current hindrance to understanding the biological roles of ecDNA is the lack of available cell line model systems with experimental cytogenetic data that confirm ecDNA status. Although several recent landmark studies have identified numerous cell lines and tumor models with ecDNA, the current sample size limits our ability to detect ecDNA-driven molecular differences due to limitations in power. Increasing the number of model systems that are known to express ecDNA would provide new avenues for understanding the fundamental underpinnings of ecDNA biology and would unlock a wealth of potential targeting strategies for ecDNA-driven cancers. To bridge this gap, we created CytoCellDB, a resource that provides karyotype annotations, including ecDNA status, and leverages publicly available global cell line data from the Cancer Dependency Map (DepMap) and the Cancer Cell Line Encyclopedia (CCLE). We expanded the total number of cancer cell lines with ecDNA annotations to 632, or 34% of the cell lines in CCLE/DepMap. Of these, 154 cell lines express ecDNA, which is a 240% increase from the current sample size. We demonstrate that a strength of our framework is the ability to interrogate ecDNA, and the compendium of other chromosomal aberrations, in the context of cancer-specific vulnerabilities, drug sensitivities, and other multi-omic features (genomics, transcriptomics, methylation, proteomics). We anticipate that this resource will lower the barrier to systematic, population-scale discoveries related to ecDNA and will provide insights into strategies and best practices for determining novel therapeutics that overcome ecDNA-mediated drug resistance. Citation Format: Liz Brunk. CytoCellDB: A gold standard database for classification and analysis of extrachromosomal DNA in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7348.