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Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma

Item Type:Article
Title:Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma
Creators Name:Koche, R.P. and Rodriguez-Fos, E. and Helmsauer, K. and Burkert, M. and MacArthur, I.C. and Maag, J. and Chamorro, R. and Munoz-Perez, N. and Puiggròs, M. and Dorado Garcia, H. and Bei, Y. and Röefzaad, C. and Bardinet, V. and Szymansky, A. and Winkler, A. and Thole, T. and Timme, N. and Kasack, K. and Fuchs, S. and Klironomos, F. and Thiessen, N. and Blanc, E. and Schmelz, K. and Künkele, A. and Hundsdörfer, P. and Rosswog, C. and Theissen, J. and Beule, D. and Deubzer, H. and Sauer, S. and Toedling, J. and Fischer, M. and Hertwig, F. and Schwarz, R.F. and Eggert, A. and Torrents, D. and Schulte, J.H. and Henssen, A.G.
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.
Keywords:Carcinogenesis, Circular DNA, Cultured Tumor Cells, Extrachromosomal Inheritance, Gene Rearrangement, Genetic Recombination, Human Genome, Neuroblastoma, Oncogenes
Source:Nature Genetics
ISSN:1061-4036
Publisher:Nature Publishing Group
Volume:52
Number:1
Page Range:29-34
Date:January 2020
Additional Information:Erratum in Nat Genet 2020 Feb 27 (in Press).
Official Publication:https://doi.org/10.1038/s41588-019-0547-z
PubMed:View item in PubMed

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