dc.contributor.author
Helmsauer, Konstantin
dc.contributor.author
Valieva, Maria E.
dc.contributor.author
Ali, Salaheddine
dc.contributor.author
Chamorro González, Rocío
dc.contributor.author
Schöpflin, Robert
dc.contributor.author
Röefzaad, Claudia
dc.contributor.author
Bei, Yi
dc.contributor.author
Dorado Garcia, Heathcliff
dc.contributor.author
Rodriguez-Fos, Elias
dc.contributor.author
Puiggròs, Montserrat
dc.contributor.author
Kasack, Katharina
dc.contributor.author
Haase, Kerstin
dc.contributor.author
Keskeny, Csilla
dc.contributor.author
Chen, Celine Y.
dc.contributor.author
Kuschel, Luis P.
dc.contributor.author
Euskirchen, Philipp
dc.contributor.author
Heinrich, Verena
dc.contributor.author
Robson, Michael I.
dc.contributor.author
Rosswog, Carolina
dc.contributor.author
Toedling, Joern
dc.contributor.author
Szymansky, Annabell
dc.contributor.author
Hertwig, Falk
dc.contributor.author
Fischer, Matthias
dc.contributor.author
Torrents, David
dc.contributor.author
Eggert, Angelika
dc.contributor.author
Schulte, Johannes H.
dc.contributor.author
Mundlos, Stefan
dc.contributor.author
Henssen, Anton G.
dc.contributor.author
Koche, Richard P.
dc.date.accessioned
2022-06-07T13:00:44Z
dc.date.available
2022-06-07T13:00:44Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/35231
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-34949
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.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
Base Sequence
en
dc.subject
Cell Line, Tumor
en
dc.subject
Chromosomes, Human
en
dc.subject
DNA Methylation
en
dc.subject
DNA, Circular
en
dc.subject
Enhancer Elements, Genetic
en
dc.subject
Epigenesis, Genetic
en
dc.subject
Kaplan-Meier Estimate
en
dc.subject
N-Myc Proto-Oncogene Protein
en
dc.subject
Nanopore Sequencing
en
dc.subject
Neuroblastoma
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Enhancer hijacking determines extrachromosomal circular MYCN amplicon architecture in neuroblastoma
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
5823
dcterms.bibliographicCitation.doi
10.1038/s41467-020-19452-y
dcterms.bibliographicCitation.journaltitle
Nature Communications
dcterms.bibliographicCitation.originalpublishername
Springer Nature
dcterms.bibliographicCitation.volume
11
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.funding
Springer Nature DEAL
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
33199677
dcterms.isPartOf.eissn
2041-1723