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| Home > Publications database > Parallel sequencing of extrachromosomal circular DNAs and transcriptomes in single cancer cells. |
| Home > Publications database > Parallel sequencing of extrachromosomal circular DNAs and transcriptomes in single cancer cells. |
| Journal Article | DKFZ-2023-00881 |
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2023
Macmillan Publishers Limited, part of Springer Nature
London
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Please use a persistent id in citations: doi:10.1038/s41588-023-01386-y
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.
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