000131790 001__ 131790
000131790 005__ 20240229105013.0
000131790 0247_ $$2doi$$a10.1038/nature25169
000131790 0247_ $$2pmid$$apmid:29258295
000131790 0247_ $$2ISSN$$a0028-0836
000131790 0247_ $$2ISSN$$a1476-4687
000131790 0247_ $$2altmetric$$aaltmetric:30719581
000131790 037__ $$aDKFZ-2018-00087
000131790 041__ $$aeng
000131790 082__ $$a070
000131790 1001_ $$aMack, Stephen C$$b0
000131790 245__ $$aTherapeutic targeting of ependymoma as informed by oncogenic enhancer profiling.
000131790 260__ $$aLondon [u.a.]$$bNature Publ. Group$$c2018
000131790 3367_ $$2DRIVER$$aarticle
000131790 3367_ $$2DataCite$$aOutput Types/Journal article
000131790 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1677760963_19615$$xLetter
000131790 3367_ $$2BibTeX$$aARTICLE
000131790 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000131790 3367_ $$00$$2EndNote$$aJournal Article
000131790 520__ $$aGenomic sequencing has driven precision-based oncology therapy; however, the genetic drivers of many malignancies remain unknown or non-targetable, so alternative approaches to the identification of therapeutic leads are necessary. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Intracranial ependymomas are segregated on the basis of anatomical location (supratentorial region or posterior fossa) and further divided into distinct molecular subgroups that reflect differences in the age of onset, gender predominance and response to therapy. The most common and aggressive subgroup, posterior fossa ependymoma group A (PF-EPN-A), occurs in young children and appears to lack recurrent somatic mutations. Conversely, posterior fossa ependymoma group B (PF-EPN-B) tumours display frequent large-scale copy number gains and losses but have favourable clinical outcomes. More than 70% of supratentorial ependymomas are defined by highly recurrent gene fusions in the NF-κB subunit gene RELA (ST-EPN-RELA), and a smaller number involve fusion of the gene encoding the transcriptional activator YAP1 (ST-EPN-YAP1). Subependymomas, a distinct histologic variant, can also be found within the supratetorial and posterior fossa compartments, and account for the majority of tumours in the molecular subgroups ST-EPN-SE and PF-EPN-SE. Here we describe mapping of active chromatin landscapes in 42 primary ependymomas in two non-overlapping primary ependymoma cohorts, with the goal of identifying essential super-enhancer-associated genes on which tumour cells depend. Enhancer regions revealed putative oncogenes, molecular targets and pathways; inhibition of these targets with small molecule inhibitors or short hairpin RNA diminished the proliferation of patient-derived neurospheres and increased survival in mouse models of ependymomas. Through profiling of transcriptional enhancers, our study provides a framework for target and drug discovery in other cancers that lack known genetic drivers and are therefore difficult to treat.
000131790 536__ $$0G:(DE-HGF)POF3-312$$a312 - Functional and structural genomics (POF3-312)$$cPOF3-312$$fPOF III$$x0
000131790 588__ $$aDataset connected to CrossRef, PubMed,
000131790 7001_ $$0P:(DE-He78)a7c1bbac024fa232d9c6b78443328d9d$$aPajtler, Kristian$$b1$$eFirst author
000131790 7001_ $$0P:(DE-He78)082dd3179733e3e716a58eb90f418a78$$aChavez, Lukas$$b2$$eFirst author
000131790 7001_ $$0P:(DE-He78)34b3639de467b2c700920d7cbc3d2110$$aOkonechnikov, Konstantin$$b3
000131790 7001_ $$aBertrand, Kelsey C$$b4
000131790 7001_ $$aWang, Xiuxing$$b5
000131790 7001_ $$0P:(DE-He78)df8660bc5aba525f7fb6dba4aac15c1c$$aErkek, Serap$$b6
000131790 7001_ $$aFederation, Alexander$$b7
000131790 7001_ $$aSong, Anne$$b8
000131790 7001_ $$aLee, Christine$$b9
000131790 7001_ $$aWang, Xin$$b10
000131790 7001_ $$aMcDonald, Laura$$b11
000131790 7001_ $$aMorrow, James J$$b12
000131790 7001_ $$aSaiakhova, Alina$$b13
000131790 7001_ $$aSin-Chan, Patrick$$b14
000131790 7001_ $$aWu, Qiulian$$b15
000131790 7001_ $$aMichaelraj, Kulandaimanuvel Antony$$b16
000131790 7001_ $$aMiller, Tyler E$$b17
000131790 7001_ $$aHubert, Christopher G$$b18
000131790 7001_ $$aRyzhova, Marina$$b19
000131790 7001_ $$aGarzia, Livia$$b20
000131790 7001_ $$aDonovan, Laura$$b21
000131790 7001_ $$aDombrowski, Stephen$$b22
000131790 7001_ $$aFactor, Daniel C$$b23
000131790 7001_ $$aLuu, Betty$$b24
000131790 7001_ $$aValentim, Claudia L L$$b25
000131790 7001_ $$aGimple, Ryan C$$b26
000131790 7001_ $$aMorton, Andrew$$b27
000131790 7001_ $$aKim, Leo$$b28
000131790 7001_ $$aPrager, Briana C$$b29
000131790 7001_ $$aLee, John J Y$$b30
000131790 7001_ $$aWu, Xiaochong$$b31
000131790 7001_ $$aZuccaro, Jennifer$$b32
000131790 7001_ $$aThompson, Yuan$$b33
000131790 7001_ $$aHolgado, Borja L$$b34
000131790 7001_ $$aReimand, Jüri$$b35
000131790 7001_ $$aKe, Susan Q$$b36
000131790 7001_ $$aTropper, Adam$$b37
000131790 7001_ $$aLai, Sisi$$b38
000131790 7001_ $$aVijayarajah, Senthuran$$b39
000131790 7001_ $$aDoan, Sylvia$$b40
000131790 7001_ $$aMahadev, Vaidehi$$b41
000131790 7001_ $$aMiñan, Ana Fernandez$$b42
000131790 7001_ $$0P:(DE-He78)932918ed0e8d8790a81235528019a8e0$$aGröbner, Susanne$$b43
000131790 7001_ $$aLienhard, Matthias$$b44
000131790 7001_ $$0P:(DE-He78)1beba8f953e7ae7e96e8d3e9a48f10f7$$aZapatka, Marc$$b45
000131790 7001_ $$0P:(DE-He78)c16f26d78779ca1c53b6939e7a5ce788$$aHuang, Zhiqin$$b46
000131790 7001_ $$aAldape, Kenneth D$$b47
000131790 7001_ $$aCarcaboso, Angel M$$b48
000131790 7001_ $$aHoughton, Peter J$$b49
000131790 7001_ $$aKeir, Stephen T$$b50
000131790 7001_ $$0P:(DE-He78)0be2f86573954f87e97f8a4dbb05cb0f$$aMilde, Till$$b51
000131790 7001_ $$0P:(DE-He78)046fd145f1008f83f6236580727bbc0f$$aWitt, Hendrik$$b52
000131790 7001_ $$aLi, Yan$$b53
000131790 7001_ $$aLi, Chao-Jun$$b54
000131790 7001_ $$aBian, Xiu-Wu$$b55
000131790 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b56
000131790 7001_ $$aScott, Ian$$b57
000131790 7001_ $$aSingh, Sheila K$$b58
000131790 7001_ $$aHuang, Annie$$b59
000131790 7001_ $$aDirks, Peter B$$b60
000131790 7001_ $$aBouffet, Eric$$b61
000131790 7001_ $$aBradner, James E$$b62
000131790 7001_ $$aRamaswamy, Vijay$$b63
000131790 7001_ $$aJabado, Nada$$b64
000131790 7001_ $$aRutka, James T$$b65
000131790 7001_ $$aNorthcott, Paul A$$b66
000131790 7001_ $$aLupien, Mathieu$$b67
000131790 7001_ $$0P:(DE-He78)e13b4363c5fe858044ef8a39c02c870c$$aLichter, Peter$$b68
000131790 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b69
000131790 7001_ $$aScacheri, Peter C$$b70
000131790 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b71
000131790 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b72$$eLast author
000131790 7001_ $$aTaylor, Michael D$$b73
000131790 7001_ $$aRich, Jeremy N$$b74
000131790 773__ $$0PERI:(DE-600)1413423-8$$a10.1038/nature25169$$gVol. 553, no. 7686, p. 101 - 105$$n7686$$p101 - 105$$tNature <London>$$v553$$x1476-4687$$y2018
000131790 909CO $$ooai:inrepo02.dkfz.de:131790$$pVDB
000131790 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)a7c1bbac024fa232d9c6b78443328d9d$$aDeutsches Krebsforschungszentrum$$b1$$kDKFZ
000131790 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)082dd3179733e3e716a58eb90f418a78$$aDeutsches Krebsforschungszentrum$$b2$$kDKFZ
000131790 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)34b3639de467b2c700920d7cbc3d2110$$aDeutsches Krebsforschungszentrum$$b3$$kDKFZ
000131790 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)df8660bc5aba525f7fb6dba4aac15c1c$$aDeutsches Krebsforschungszentrum$$b6$$kDKFZ
000131790 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)932918ed0e8d8790a81235528019a8e0$$aDeutsches Krebsforschungszentrum$$b43$$kDKFZ
000131790 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)1beba8f953e7ae7e96e8d3e9a48f10f7$$aDeutsches Krebsforschungszentrum$$b45$$kDKFZ
000131790 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)c16f26d78779ca1c53b6939e7a5ce788$$aDeutsches Krebsforschungszentrum$$b46$$kDKFZ
000131790 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)0be2f86573954f87e97f8a4dbb05cb0f$$aDeutsches Krebsforschungszentrum$$b51$$kDKFZ
000131790 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)046fd145f1008f83f6236580727bbc0f$$aDeutsches Krebsforschungszentrum$$b52$$kDKFZ
000131790 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)551bb92841f634070997aa168d818492$$aDeutsches Krebsforschungszentrum$$b56$$kDKFZ
000131790 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)e13b4363c5fe858044ef8a39c02c870c$$aDeutsches Krebsforschungszentrum$$b68$$kDKFZ
000131790 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aDeutsches Krebsforschungszentrum$$b69$$kDKFZ
000131790 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aDeutsches Krebsforschungszentrum$$b71$$kDKFZ
000131790 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aDeutsches Krebsforschungszentrum$$b72$$kDKFZ
000131790 9131_ $$0G:(DE-HGF)POF3-312$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vFunctional and structural genomics$$x0
000131790 9141_ $$y2018
000131790 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz
000131790 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000131790 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000131790 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000131790 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bNATURE : 2015
000131790 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search
000131790 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC
000131790 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000131790 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000131790 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000131790 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000131790 915__ $$0StatID:(DE-HGF)1060$$2StatID$$aDBCoverage$$bCurrent Contents - Agriculture, Biology and Environmental Sciences
000131790 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000131790 915__ $$0StatID:(DE-HGF)1150$$2StatID$$aDBCoverage$$bCurrent Contents - Physical, Chemical and Earth Sciences
000131790 915__ $$0StatID:(DE-HGF)1040$$2StatID$$aDBCoverage$$bZoological Record
000131790 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000131790 915__ $$0StatID:(DE-HGF)9930$$2StatID$$aIF >= 30$$bNATURE : 2015
000131790 9201_ $$0I:(DE-He78)B062-20160331$$kB062$$lB062 Pädiatrische Neuroonkologie$$x0
000131790 9201_ $$0I:(DE-He78)L101-20160331$$kL101$$lDKTK Heidelberg$$x1
000131790 9201_ $$0I:(DE-He78)B060-20160331$$kB060$$lB060 Molekulare Genetik$$x2
000131790 9201_ $$0I:(DE-He78)G340-20160331$$kG340$$lKKE Pädiatrische Onkologie$$x3
000131790 9201_ $$0I:(DE-He78)G380-20160331$$kG380$$lKKE Neuropathologie$$x4
000131790 980__ $$ajournal
000131790 980__ $$aVDB
000131790 980__ $$aI:(DE-He78)B062-20160331
000131790 980__ $$aI:(DE-He78)L101-20160331
000131790 980__ $$aI:(DE-He78)B060-20160331
000131790 980__ $$aI:(DE-He78)G340-20160331
000131790 980__ $$aI:(DE-He78)G380-20160331
000131790 980__ $$aUNRESTRICTED