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Parallel sequencing of extrachromosomal circular DNAs and transcriptomes in single cancer cells

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Item Type:Article
Title:Parallel sequencing of extrachromosomal circular DNAs and transcriptomes in single cancer cells
Creators Name:Chamorro González, R. and Conrad, T. and Stöber, M.C. and Xu, R. and Giurgiu, M. and Rodriguez-Fos, E. and Kasack, K. and Brückner, L. and van Leen, E. and Helmsauer, K. and Dorado Garcia, H. and Stefanova, M.E. and Hung, K.L. and Bei, Y. and Schmelz, K. and Lodrini, M. and Mundlos, S. and Chang, H.Y. and Deubzer, H.E. and Sauer, S. and Eggert, A. and Schulte, J.H. and Schwarz, R.F. and Haase, K. and Koche, R.P. and Henssen, A.G.
Abstract:Extrachromosomal DNAs (ecDNAs) are common in cancer, but many questions about their origin, structural dynamics and impact on intratumor heterogeneity are still unresolved. Here we describe single-cell extrachromosomal circular DNA and transcriptome sequencing (scEC&T-seq), a method for parallel sequencing of circular DNAs and full-length mRNA from single cells. By applying scEC&T-seq to cancer cells, we describe intercellular differences in ecDNA content while investigating their structural heterogeneity and transcriptional impact. Oncogene-containing ecDNAs were clonally present in cancer cells and drove intercellular oncogene expression differences. In contrast, other small circular DNAs were exclusive to individual cells, indicating differences in their selection and propagation. Intercellular differences in ecDNA structure pointed to circular recombination as a mechanism of ecDNA evolution. These results demonstrate scEC&T-seq as an approach to systematically characterize both small and large circular DNA in cancer cells, which will facilitate the analysis of these DNA elements in cancer and beyond.
Keywords:DNA, Circular DNA, Neoplasms, Oncogenes, Transcriptome Genetics
Source:Nature Genetics
ISSN:1061-4036
Publisher:Nature Publishing Group
Volume:55
Number:5
Page Range:880-890
Date:May 2023
Official Publication:https://doi.org/10.1038/s41588-023-01386-y
PubMed:View item in PubMed

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