Koche, Richard P., Rodriguez-Fos, Elias ORCID: 0000-0002-2555-0178, Helmsauer, Konstantin ORCID: 0000-0003-0773-4114, Burkert, Martin ORCID: 0000-0002-6721-9985, MacArthur, Ian C., Maag, Jesper, Chamorro, Rocio, Munoz-Perez, Natalia, Puiggros, Montserrat, Dorado Garcia, Heathcliff, Bei, Yi, Roeefzaad, Claudia, Bardinet, Victor, Szymansky, Annabell, Winkler, Annika, Thole, Theresa, Timme, Natalie, Kasack, Katharina, Fuchs, Steffen ORCID: 0000-0001-9619-4329, Klironomos, Filippos, Thiessen, Nina, Blanc, Eric, Schmelz, Karin, Kuenkele, Annette, Hundsdoerfer, Patrick, Rosswog, Carolina, Theissen, Jessica, Beule, Dieter, Deubzer, Hedwig, Sauer, Sascha, Toedling, Joern, Fischer, Matthias, Hertwig, Falk ORCID: 0000-0003-4784-6516, Schwarz, Roland F., Eggert, Angelika ORCID: 0000-0003-3476-8184, Torrents, David, Schulte, Johannes H. and Henssen, Anton G. (2020). Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma. Nature Genet., 52 (1). S. 29 - 38. BERLIN: NATURE RESEARCH. ISSN 1546-1718

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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. Combined genomic and transcriptomic approaches identify the landscape of extrachromosomal circular DNA in neuroblastoma and reveal that extrachromosomal circular DNA is a major source of somatic rearrangements.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Koche, Richard P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rodriguez-Fos, EliasUNSPECIFIEDorcid.org/0000-0002-2555-0178UNSPECIFIED
Helmsauer, KonstantinUNSPECIFIEDorcid.org/0000-0003-0773-4114UNSPECIFIED
Burkert, MartinUNSPECIFIEDorcid.org/0000-0002-6721-9985UNSPECIFIED
MacArthur, Ian C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maag, JesperUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chamorro, RocioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Munoz-Perez, NataliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Puiggros, MontserratUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dorado Garcia, HeathcliffUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bei, YiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roeefzaad, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bardinet, VictorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Szymansky, AnnabellUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Winkler, AnnikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thole, TheresaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Timme, NatalieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kasack, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fuchs, SteffenUNSPECIFIEDorcid.org/0000-0001-9619-4329UNSPECIFIED
Klironomos, FilipposUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thiessen, NinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blanc, EricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmelz, KarinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuenkele, AnnetteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hundsdoerfer, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosswog, CarolinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Theissen, JessicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beule, DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deubzer, HedwigUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sauer, SaschaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toedling, JoernUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hertwig, FalkUNSPECIFIEDorcid.org/0000-0003-4784-6516UNSPECIFIED
Schwarz, Roland F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eggert, AngelikaUNSPECIFIEDorcid.org/0000-0003-3476-8184UNSPECIFIED
Torrents, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulte, Johannes H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Henssen, Anton G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-351593
DOI: 10.1038/s41588-019-0547-z
Journal or Publication Title: Nature Genet.
Volume: 52
Number: 1
Page Range: S. 29 - 38
Date: 2020
Publisher: NATURE RESEARCH
Place of Publication: BERLIN
ISSN: 1546-1718
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HOMOGENEOUSLY STAINING REGIONS; COPY NUMBER; AMPLIFICATION; CANCER; EVOLUTION; MICRODNAS; TUMORSMultiple languages
Genetics & HeredityMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/35159

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