000127794 001__ 127794
000127794 005__ 20240228140950.0
000127794 0247_ $$2doi$$a10.18632/oncotarget.3377
000127794 0247_ $$2pmid$$apmid:25749049
000127794 0247_ $$2pmc$$apmc:PMC4466681
000127794 037__ $$aDKFZ-2017-03816
000127794 041__ $$aeng
000127794 082__ $$a610
000127794 1001_ $$aWilliams, Richard D$$b0
000127794 245__ $$aMultiple mechanisms of MYCN dysregulation in Wilms tumour.
000127794 260__ $$a[S.l.]$$bImpact Journals LLC$$c2015
000127794 3367_ $$2DRIVER$$aarticle
000127794 3367_ $$2DataCite$$aOutput Types/Journal article
000127794 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1508923398_22424
000127794 3367_ $$2BibTeX$$aARTICLE
000127794 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000127794 3367_ $$00$$2EndNote$$aJournal Article
000127794 520__ $$aGenomic gain of the proto-oncogene transcription factor gene MYCN is associated with poor prognosis in several childhood cancers. Here we present a comprehensive copy number analysis of MYCN in Wilms tumour (WT), demonstrating that gain of this gene is associated with anaplasia and with poorer relapse-free and overall survival, independent of histology. Using whole exome and gene-specific sequencing, together with methylation and expression profiling, we show that MYCN is targeted by other mechanisms, including a recurrent somatic mutation, P44L, and specific DNA hypomethylation events associated with MYCN overexpression in tumours with high risk histologies. We describe parallel evolution of genomic copy number gain and point mutation of MYCN in the contralateral tumours of a remarkable bilateral case in which independent contralateral mutations of TP53 also evolve over time. We report a second bilateral case in which MYCN gain is a germline aberration. Our results suggest a significant role for MYCN dysregulation in the molecular biology of Wilms tumour. We conclude that MYCN gain is prognostically significant, and suggest that the novel P44L somatic variant is likely to be an activating mutation.
000127794 536__ $$0G:(DE-HGF)POF3-312$$a312 - Functional and structural genomics (POF3-312)$$cPOF3-312$$fPOF III$$x0
000127794 588__ $$aDataset connected to CrossRef, PubMed,
000127794 650_7 $$2NLM Chemicals$$aProto-Oncogene Proteins c-myc
000127794 650_7 $$2NLM Chemicals$$aTP53 protein, human
000127794 650_7 $$2NLM Chemicals$$aTumor Suppressor Protein p53
000127794 7001_ $$aChagtai, Tasnim$$b1
000127794 7001_ $$aAlcaide-German, Marisa$$b2
000127794 7001_ $$aApps, John$$b3
000127794 7001_ $$aWegert, Jenny$$b4
000127794 7001_ $$aPopov, Sergey$$b5
000127794 7001_ $$aVujanic, Gordan$$b6
000127794 7001_ $$avan Tinteren, Harm$$b7
000127794 7001_ $$avan den Heuvel-Eibrink, Marry M$$b8
000127794 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b9$$udkfz
000127794 7001_ $$ade Kraker, Jan$$b10
000127794 7001_ $$aGisselsson, David$$b11
000127794 7001_ $$aGraf, Norbert$$b12
000127794 7001_ $$aGessler, Manfred$$b13
000127794 7001_ $$aPritchard-Jones, Kathy$$b14
000127794 773__ $$0PERI:(DE-600)2560162-3$$a10.18632/oncotarget.3377$$gVol. 6, no. 9, p. 7232 - 7243$$n9$$p7232 - 7243$$tOncoTarget$$v6$$x1949-2553$$y2015
000127794 909CO $$ooai:inrepo02.dkfz.de:127794$$pVDB
000127794 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aDeutsches Krebsforschungszentrum$$b9$$kDKFZ
000127794 9131_ $$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$$x0
000127794 9141_ $$y2015
000127794 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bONCOTARGET : 2015
000127794 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000127794 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000127794 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000127794 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000127794 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000127794 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000127794 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000127794 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bONCOTARGET : 2015
000127794 9201_ $$0I:(DE-He78)B062-20160331$$kB062$$lPädiatrische Neuroonkologie$$x0
000127794 980__ $$ajournal
000127794 980__ $$aVDB
000127794 980__ $$aI:(DE-He78)B062-20160331
000127794 980__ $$aUNRESTRICTED