Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma Research Letter
| Authors: | Koche, R. P.; Rodriguez-Fos, E.; Helmsauer, K.; Burkert, M.; MacArthur, I. C.; Maag, J.; Chamorro, R.; Munoz-Perez, N.; Puiggròs, M.; Garcia, H. D.; Bei, Y.; Röefzaad, C.; Bardinet, V.; Szymansky, A.; Winkler, A.; Thole, T.; Timme, N.; Kasack, K.; Fuchs, S.; Klironomos, F.; Thiessen, N.; Blanc, E.; Schmelz, K.; Künkele, A.; Hundsdörfer, P.; Rosswog, C.; Theissen, J.; Beule, D.; Deubzer, H.; Sauer, S.; Toedling, J.; Fischer, M.; Hertwig, F.; Schwarz, R. F.; Eggert, A.; Torrents, D.; Schulte, J. H.; Henssen, A. G. |
| Title: | Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma |
| Abstract: | Extrachromosomal circularization of DNA is an important genomic feature in cancer. However, the structure, composition and genome-wide frequency of extrachromosomal circular DNA have not yet been profiled extensively. Here, we combine genomic and transcriptomic approaches to describe the landscape of extrachromosomal circular DNA in neuroblastoma, a tumor arising in childhood from primitive cells of the sympathetic nervous system. Our analysis identifies and characterizes a wide catalog of somatically acquired and undescribed extrachromosomal circular DNAs. Moreover, we find that extrachromosomal circular DNAs are an unanticipated major source of somatic rearrangements, contributing to oncogenic remodeling through chimeric circularization and reintegration of circular DNA into the linear genome. Cancer-causing lesions can emerge out of circle-derived rearrangements and are associated with adverse clinical outcome. It is highly probable that circle-derived rearrangements represent an ongoing mutagenic process. Thus, extrachromosomal circular DNAs represent a multihit mutagenic process, with important functional and clinical implications for the origins of genomic remodeling in cancer. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc. |
| Keywords: | controlled study; human cell; letter; gene amplification; gene frequency; carcinogenesis; cancer genetics; neuroblastoma; myc protein; genome; real time polymerase chain reaction; chromosome 13; chromosome 2; dna determination; mutagenesis; rna sequence; transcription initiation site; basic helix loop helix transcription factor; copy number variation; clinical outcome; lymphoma cell line; circular dna; dna end joining repair; sanger sequencing; human; priority journal; whole genome sequencing; neuroblastoma cell line; extrachromosomal dna |
| Journal Title: | Nature Genetics |
| Volume: | 52 |
| Issue: | 1 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2020-01-01 |
| Start Page: | 29 |
| End Page: | 34 |
| Language: | English |
| DOI: | 10.1038/s41588-019-0547-z |
| PUBMED: | 31844324 |
| PROVIDER: | scopus |
| PMCID: | PMC7008131 |
| DOI/URL: | |
| Notes: | Source: Scopus -- Correction issued, see DOI 10.1038/s41588-020-0598-1 |
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