Enhancer hijacking determines extrachromosomal circular MYCN amplicon architecture in neuroblastoma

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• dc.contributor.author Helmsauer, Konstantin
• dc.contributor.author Rodriguez-Fos, Elias
• dc.contributor.author Puiggròs, Montserrat
• dc.contributor.author Torrents, David
• dc.contributor.author Koche, Richard P.
• dc.date.accessioned 2022-05-20T05:52:16Z
• dc.date.available 2022-05-20T05:52:16Z
• dc.date.issued 2020
• dc.description.abstract MYCN amplification drives one in six cases of neuroblastoma. The supernumerary gene copies are commonly found on highly rearranged, extrachromosomal circular DNA (ecDNA). The exact amplicon structure has not been described thus far and the functional relevance of its rearrangements is unknown. Here, we analyze the MYCN amplicon structure using short-read and Nanopore sequencing and its chromatin landscape using ChIP-seq, ATAC-seq and Hi-C. This reveals two distinct classes of amplicons which explain the regulatory requirements for MYCN overexpression. The first class always co-amplifies a proximal enhancer driven by the noradrenergic core regulatory circuit (CRC). The second class of MYCN amplicons is characterized by high structural complexity, lacks key local enhancers, and instead contains distal chromosomal fragments harboring CRC-driven enhancers. Thus, ectopic enhancer hijacking can compensate for the loss of local gene regulatory elements and explains a large component of the structural diversity observed in MYCN amplification.
• dc.description.sponsorship Open Access funding enabled and organized by Projekt DEAL. This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. A.G.H. is supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 398299703 Helmsauer is supported by Boehringer Ingelheim Fonds. This work was also supported by the TransTumVar project - PN013600
• dc.format.mimetype application/pdf
• dc.identifier.citation Helmsauer K, Valieva ME, Ali S, Chamorro González R, Schöplin R, Röefzaad C et al. Enhancer hijacking determines extrachromosomal circular MYCN amplicon architecture in neuroblastoma. Nat Commun. 2020 Nov 16;11(1):5823. DOI:10.1038/s41467-020-19452-y
• dc.identifier.doi http://dx.doi.org/10.1038/s41467-020-19452-y
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/53179
• dc.language.iso eng
• dc.publisher Nature Research
• dc.rights © Konstantin Helmsauer et al. 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.other Genètica
• dc.subject.other Neuroblastoma
• dc.title Enhancer hijacking determines extrachromosomal circular MYCN amplicon architecture in neuroblastoma
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion