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@ARTICLE{Gartlgruber:166292,
author = {M. Gartlgruber$^*$ and A. K. Sharma$^*$ and A. Quintero$^*$
and D. Dreidax$^*$ and S. Jansky$^*$ and Y.-G. Park$^*$ and
S. Kreth$^*$ and J. Meder and D. Doncevic$^*$ and P. Saary
and U. H. Toprak$^*$ and N. Ishaque and E. Afanasyeva$^*$
and E. Wecht$^*$ and J. Koster and R. Versteeg and T.
Grünewald$^*$ and D. T. W. Jones$^*$ and S. M. Pfister$^*$
and K.-O. Henrich$^*$ and J. van Nes and C. Herrmann and F.
Westermann$^*$},
title = {{S}uper enhancers define regulatory subtypes and cell
identity in neuroblastoma},
journal = {Nature cancer},
volume = {2},
issn = {2662-1347},
address = {London},
publisher = {Nature Research},
reportid = {DKFZ-2020-02785},
pages = {114–128},
year = {2021},
note = {#EA:B087#LA:B087# VOL 2 | JANUARy 2021 | 114–128},
abstract = {Half of the children diagnosed with neuroblastoma (NB) have
high-risk disease, disproportionately contributing to
overall childhood cancer-related deaths. In addition to
recurrent gene mutations, there is increasing evidence
supporting the role of epigenetic deregulation in disease
pathogenesis. Yet, comprehensive cis-regulatory network
descriptions from NB are lacking. Here, using genome-wide
H3K27ac profiles across 60 NBs, covering the different
clinical and molecular subtypes, we identified four major
super-enhancer-driven epigenetic subtypes and their
underlying master regulatory networks. Three of these
subtypes recapitulated known clinical groups; namely,
MYCN-amplified, MYCN non-amplified high-risk and MYCN
non-amplified low-risk NBs. The fourth subtype, exhibiting
mesenchymal characteristics, shared cellular identity with
multipotent Schwann cell precursors, was induced by RAS
activation and was enriched in relapsed disease. Notably,
CCND1, an essential gene in NB, was regulated by both
mesenchymal and adrenergic regulatory networks converging on
distinct super-enhancer modules. Overall, this study reveals
subtype-specific super-enhancer regulation in NBs.},
cin = {B087 / B410 / HD01 / B360 / B062},
ddc = {610},
cid = {I:(DE-He78)B087-20160331 / I:(DE-He78)B410-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)B360-20160331 /
I:(DE-He78)B062-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
doi = {10.1038/s43018-020-00145-w},
url = {https://inrepo02.dkfz.de/record/166292},
}