TY - JOUR TI - Enhancer hijacking determines extrachromosomal circular MYCN amplicon architecture in neuroblastoma AU - Helmsauer, Konstantin AU - Valieva, Maria E. AU - Ali, Salaheddine AU - Chamorro González, Rocío AU - Schöpflin, Robert AU - Röefzaad, Claudia AU - Bei, Yi AU - Dorado Garcia, Heathcliff AU - Rodriguez-Fos, Elias AU - Puiggròs, Montserrat AU - Kasack, Katharina AU - Haase, Kerstin AU - Keskeny, Csilla AU - Chen, Celine Y. AU - Kuschel, Luis P. AU - Euskirchen, Philipp AU - Heinrich, Verena AU - Robson, Michael I. AU - Rosswog, Carolina AU - Toedling, Joern AU - Szymansky, Annabell AU - Hertwig, Falk AU - Fischer, Matthias AU - Torrents, David AU - Eggert, Angelika AU - Schulte, Johannes H. AU - Mundlos, Stefan AU - Henssen, Anton G. AU - Koche, Richard P. T2 - Nature Communications AB - 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. DA - 2020/11/16/ PY - 2020 DO - 10.1038/s41467-020-19452-y DP - www.nature.com VL - 11 IS - 1 SP - 5823 LA - en SN - 2041-1723 UR - https://www.nature.com/articles/s41467-020-19452-y Y2 - 2020/11/16/22:17:16 ER -