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000166292 1001_ $$0P:(DE-He78)5190aa0a28a0d3d663954c463290e4c1$$aGartlgruber, Moritz$$b0$$eFirst author
000166292 245__ $$aSuper enhancers define regulatory subtypes and cell identity in neuroblastoma
000166292 260__ $$aLondon$$bNature Research$$c2021
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000166292 500__ $$a#EA:B087#LA:B087# VOL 2 | JANUARy 2021 | 114–128
000166292 520__ $$aHalf 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.
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000166292 7001_ $$00000-0002-3959-805X$$aQuintero, Andrés$$b2
000166292 7001_ $$0P:(DE-He78)00d281bd33b8c1254cbe4f048dbfaa14$$aDreidax, Daniel$$b3
000166292 7001_ $$0P:(DE-He78)0d2f8ea0917f8fb1a5668af95b36bd8b$$aJansky, Selina$$b4
000166292 7001_ $$0P:(DE-He78)1dca75c95409803396496586047ae881$$aPark, Young-Gyu$$b5
000166292 7001_ $$0P:(DE-He78)21d657d65d4ad0fd8b0bbfe10fa65172$$aKreth, Sina$$b6
000166292 7001_ $$0P:(DE-He78)196067e8183923fe7b74eb55f85cb503$$aMeder, Johanna$$b7
000166292 7001_ $$0P:(DE-He78)dd50491ca9154efffd0f52480e15f592$$aDoncevic, Daria$$b8
000166292 7001_ $$aSaary, Paul$$b9
000166292 7001_ $$0P:(DE-He78)cd8295952c28dc5b483b5ba9386a5669$$aToprak, Umut H.$$b10
000166292 7001_ $$aIshaque, Naveed$$b11
000166292 7001_ $$0P:(DE-He78)00a05211e3c20e831f301cbacab8e5f2$$aAfanasyeva, Elena$$b12
000166292 7001_ $$0P:(DE-He78)8f7a0515aec950d7157b3932b942503f$$aWecht, Elisa$$b13
000166292 7001_ $$00000-0002-0890-7585$$aKoster, Jan$$b14
000166292 7001_ $$00000-0001-7172-0388$$aVersteeg, Rogier$$b15
000166292 7001_ $$0P:(DE-He78)7a590ab95c6f7ba52880452da78ecd6c$$aGrünewald, Thomas$$b16
000166292 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David T. W.$$b17
000166292 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan M.$$b18
000166292 7001_ $$0P:(DE-He78)a579ca2567736066534409e732b31c91$$aHenrich, Kai-Oliver$$b19
000166292 7001_ $$00000-0001-7691-1431$$avan Nes, Johan$$b20
000166292 7001_ $$0P:(DE-HGF)0$$aHerrmann, Carl$$b21
000166292 7001_ $$0P:(DE-He78)91f32735ee876c579d63c05a7f4778dd$$aWestermann, Frank$$b22$$eLast author
000166292 773__ $$0PERI:(DE-600)3005299-3$$a10.1038/s43018-020-00145-w$$p114–128$$tNature cancer$$v2$$x2662-1347$$y2021
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