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Article: Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma

TitleEnhancer hijacking activates GFI1 family oncogenes in medulloblastoma
Authors
Issue Date2014
Citation
Nature, 2014, v. 511, n. 7510, p. 428-434 How to Cite?
AbstractMedulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer. © 2014 Macmillan Publishers Limited. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/313992
ISSN
2023 Impact Factor: 50.5
2023 SCImago Journal Rankings: 18.509
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorNorthcott, Paul A.-
dc.contributor.authorLee, Catherine-
dc.contributor.authorZichner, Thomas-
dc.contributor.authorStütz, Adrian M.-
dc.contributor.authorErkek, Serap-
dc.contributor.authorKawauchi, Daisuke-
dc.contributor.authorShih, David J.H.-
dc.contributor.authorHovestadt, Volker-
dc.contributor.authorZapatka, Marc-
dc.contributor.authorSturm, Dominik-
dc.contributor.authorJones, David T.W.-
dc.contributor.authorKool, Marcel-
dc.contributor.authorRemke, Marc-
dc.contributor.authorCavalli, Florence M.G.-
dc.contributor.authorZuyderduyn, Scott-
dc.contributor.authorBader, Gary D.-
dc.contributor.authorVandenberg, Scott-
dc.contributor.authorEsparza, Lourdes Adriana-
dc.contributor.authorRyzhova, Marina-
dc.contributor.authorWang, Wei-
dc.contributor.authorWittmann, Andrea-
dc.contributor.authorStark, Sebastian-
dc.contributor.authorSieber, Laura-
dc.contributor.authorSeker-Cin, Huriye-
dc.contributor.authorLinke, Linda-
dc.contributor.authorKratochwil, Fabian-
dc.contributor.authorJäger, Natalie-
dc.contributor.authorBuchhalter, Ivo-
dc.contributor.authorImbusch, Charles D.-
dc.contributor.authorZipprich, Gideon-
dc.contributor.authorRaeder, Benjamin-
dc.contributor.authorSchmidt, Sabine-
dc.contributor.authorDiessl, Nicolle-
dc.contributor.authorWolf, Stephan-
dc.contributor.authorWiemann, Stefan-
dc.contributor.authorBrors, Benedikt-
dc.contributor.authorLawerenz, Chris-
dc.contributor.authorEils, Jürgen-
dc.contributor.authorWarnatz, Hans Jörg-
dc.contributor.authorRisch, Thomas-
dc.contributor.authorYaspo, Marie Laure-
dc.contributor.authorWeber, Ursula D.-
dc.contributor.authorBartholomae, Cynthia C.-
dc.contributor.authorVon Kalle, Christof-
dc.contributor.authorTurányi, Eszter-
dc.contributor.authorHauser, Peter-
dc.contributor.authorSanden, Emma-
dc.contributor.authorDarabi, Anna-
dc.contributor.authorSiesjö, Peter-
dc.contributor.authorSterba, Jaroslav-
dc.contributor.authorZitterbart, Karel-
dc.contributor.authorSumerauer, David-
dc.contributor.authorVan Sluis, Peter-
dc.contributor.authorVersteeg, Rogier-
dc.contributor.authorVolckmann, Richard-
dc.contributor.authorKoster, Jan-
dc.contributor.authorSchuhmann, Martin U.-
dc.contributor.authorEbinger, Martin-
dc.contributor.authorGrimes, H. Leighton-
dc.contributor.authorRobinson, Giles W.-
dc.contributor.authorGajjar, Amar-
dc.contributor.authorMynarek, Martin-
dc.contributor.authorVon Hoff, Katja-
dc.contributor.authorRutkowski, Stefan-
dc.contributor.authorPietsch, Torsten-
dc.contributor.authorScheurlen, Wolfram-
dc.contributor.authorFelsberg, Jörg-
dc.contributor.authorReifenberger, Guido-
dc.contributor.authorKulozik, Andreas E.-
dc.contributor.authorVon Deimling, Andreas-
dc.contributor.authorWitt, Olaf-
dc.contributor.authorEils, Roland-
dc.contributor.authorGilbertson, Richard J.-
dc.contributor.authorKorshunov, Andrey-
dc.contributor.authorTaylor, Michael D.-
dc.contributor.authorLichter, Peter-
dc.contributor.authorKorbel, Jan O.-
dc.contributor.authorWechsler-Reya, Robert J.-
dc.contributor.authorPfister, Stefan M.-
dc.date.accessioned2022-07-06T11:28:45Z-
dc.date.available2022-07-06T11:28:45Z-
dc.date.issued2014-
dc.identifier.citationNature, 2014, v. 511, n. 7510, p. 428-434-
dc.identifier.issn0028-0836-
dc.identifier.urihttp://hdl.handle.net/10722/313992-
dc.description.abstractMedulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer. © 2014 Macmillan Publishers Limited. All rights reserved.-
dc.languageeng-
dc.relation.ispartofNature-
dc.titleEnhancer hijacking activates GFI1 family oncogenes in medulloblastoma-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/nature13379-
dc.identifier.pmid25043047-
dc.identifier.pmcidPMC4201514-
dc.identifier.scopuseid_2-s2.0-84904816744-
dc.identifier.volume511-
dc.identifier.issue7510-
dc.identifier.spage428-
dc.identifier.epage434-
dc.identifier.eissn1476-4687-
dc.identifier.isiWOS:000339335700038-

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