Enhancer hijacking determines intra- and extrachromosomal circular MYCN amplicon architecture in neuroblastoma
Rocio Chamorro Gonzalez,
Heathcliff Dorado Garcia,
Luis P. Kuschel,
Johannes H Schulte,
Anton G Henssen,
Richard P. Koche
Posted 20 Dec 2019
bioRxiv DOI: 10.1101/2019.12.20.875807
Posted 20 Dec 2019
MYCN amplification drives one in six cases of neuroblastoma. The supernumerary gene copies are commonly found on highly rearranged, extrachromosomal circular DNA. The exact amplicon structure has not been described thus far and the functional relevance of its rearrangements is unknown. Here, we analyzed the MYCN amplicon structure and its chromatin landscape. This revealed two distinct classes of amplicons which explain the regulatory requirements for MYCN overexpression. The first class always co-amplified a proximal enhancer driven by the noradrenergic core regulatory circuit (CRC). The second class of MYCN amplicons was characterized by high structural complexity, lacked key local enhancers, and instead contained distal chromosomal fragments, which harbored 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.
- Downloaded 881 times
- Download rankings, all-time:
- Site-wide: 14,490 out of 92,091
- In cancer biology: 418 out of 3,259
- Year to date:
- Site-wide: 3,646 out of 92,091
- Since beginning of last month:
- Site-wide: 6,449 out of 92,091
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!