Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma.
Richard P Koche, Elias Rodriguez-Fos, Konstantin Helmsauer, Martin Burkert, Ian C MacArthur, Jesper Maag, Rocio Chamorro, Natalia Munoz-Perez, Montserrat Puiggròs, Heathcliff Dorado Garcia, Yi Bei, Claudia Röefzaad, Victor Bardinet, Annabell Szymansky, Annika Winkler, Theresa Thole, Natalie Timme, Katharina Kasack, Steffen Fuchs, Filippos Klironomos, Nina Thiessen, Eric Blanc, Karin Schmelz, Annette Künkele, Patrick Hundsdörfer, Carolina Rosswog, Jessica Theissen, Dieter Beule, Hedwig Deubzer, Sascha Sauer, Joern Toedling, Matthias Fischer, Falk Hertwig, Roland F Schwarz, Angelika Eggert, David Torrents, Johannes H Schulte, Anton G Henssen
Nature genetics 2020 JanExtrachromosomal 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.
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Richard P Koche, Elias Rodriguez-Fos, Konstantin Helmsauer, Martin Burkert, Ian C MacArthur, Jesper Maag, Rocio Chamorro, Natalia Munoz-Perez, Montserrat Puiggròs, Heathcliff Dorado Garcia, Yi Bei, Claudia Röefzaad, Victor Bardinet, Annabell Szymansky, Annika Winkler, Theresa Thole, Natalie Timme, Katharina Kasack, Steffen Fuchs, Filippos Klironomos, Nina Thiessen, Eric Blanc, Karin Schmelz, Annette Künkele, Patrick Hundsdörfer, Carolina Rosswog, Jessica Theissen, Dieter Beule, Hedwig Deubzer, Sascha Sauer, Joern Toedling, Matthias Fischer, Falk Hertwig, Roland F Schwarz, Angelika Eggert, David Torrents, Johannes H Schulte, Anton G Henssen. Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma. Nature genetics. 2020 Jan;52(1):29-34
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PMID: 31844324
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