Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma.

Autor: Koche RP; Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA. kocher@mskcc.org., Rodriguez-Fos E; Barcelona Supercomputing Center, Joint Barcelona Supercomputing Center-Centre for Genomic Regulation-Institute for Research in Biomedicine Research Program in Computational Biology, Barcelona, Spain., Helmsauer K; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Burkert M; Department of Biology, Humboldt University, Berlin, Germany.; Berlin Institute of Health, Berlin, Germany.; Max Delbrück Center for Molecular Medicine, Berlin, Germany., MacArthur IC; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Maag J; Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Chamorro R; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Munoz-Perez N; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Puiggròs M; Barcelona Supercomputing Center, Joint Barcelona Supercomputing Center-Centre for Genomic Regulation-Institute for Research in Biomedicine Research Program in Computational Biology, Barcelona, Spain., Dorado Garcia H; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Bei Y; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Röefzaad C; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Bardinet V; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Szymansky A; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Winkler A; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Thole T; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Timme N; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Kasack K; German Cancer Consortium (DKTK), partner site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany., Fuchs S; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany.; Berlin Institute of Health, Berlin, Germany.; German Cancer Consortium (DKTK), partner site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany., Klironomos F; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Thiessen N; Berlin Institute of Health, Berlin, Germany., Blanc E; Berlin Institute of Health, Berlin, Germany., Schmelz K; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Künkele A; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany.; Berlin Institute of Health, Berlin, Germany.; German Cancer Consortium (DKTK), partner site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany., Hundsdörfer P; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany.; Berlin Institute of Health, Berlin, Germany.; German Cancer Consortium (DKTK), partner site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany., Rosswog C; German Cancer Consortium (DKTK), partner site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany., Theissen J; German Cancer Consortium (DKTK), partner site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany., Beule D; Berlin Institute of Health, Berlin, Germany., Deubzer H; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany.; German Cancer Consortium (DKTK), partner site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.; Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany., Sauer S; Berlin Institute of Health, Berlin, Germany., Toedling J; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Fischer M; Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne, Medical Faculty, University of Cologne, Cologne, Germany., Hertwig F; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany.; German Cancer Consortium (DKTK), partner site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany., Schwarz RF; Max Delbrück Center for Molecular Medicine, Berlin, Germany.; German Cancer Consortium (DKTK), partner site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany., Eggert A; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany.; Berlin Institute of Health, Berlin, Germany.; German Cancer Consortium (DKTK), partner site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany., Torrents D; Barcelona Supercomputing Center, Joint Barcelona Supercomputing Center-Centre for Genomic Regulation-Institute for Research in Biomedicine Research Program in Computational Biology, Barcelona, Spain.; Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain., Schulte JH; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany.; Berlin Institute of Health, Berlin, Germany.; German Cancer Consortium (DKTK), partner site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany., Henssen AG; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany. henssenlab@gmail.com.; Berlin Institute of Health, Berlin, Germany. henssenlab@gmail.com.; German Cancer Consortium (DKTK), partner site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany. henssenlab@gmail.com.; Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany. henssenlab@gmail.com.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2020 Jan; Vol. 52 (1), pp. 29-34. Date of Electronic Publication: 2019 Dec 16.
DOI: 10.1038/s41588-019-0547-z
Abstrakt: 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.
Databáze: MEDLINE
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