NORTHCOTT, Paul A., Catherine LEE, Thomas ZICHNER, Adrian M. STÜTZ, Serap ERKEK, Daisuke KAWAUCHI, David J.H. SHIH, Volker HOVESTADT, Marc ZAPATKA, Dominik STURM, David T.W. JONES, Marcel KOOL, Marc REMKE, Florence M.G. CAVALLI, Scott ZUYDERDUYN, Gary D. BADER, Scott VANDENBERG, Lourdes Adriana ESPARZA, Marina RYZHOVA, Wei WANG, Andrea WITTMANN, Sebastian STARK, Laura SIEBER, Huriye SEKER-CIN, Linda LINKE, Fabian KRATOCHWIL, Natalie JÄGER, Ivo BUCHHALTER, Charles D. IMBUSCH, Gideon ZIPPRICH, Benjamin RAEDER, Sabine SCHMIDT, Nicolle DIESSL, Stephan WOLF, Stefan WIEMANN, Benedikt BRORS, Chris LAWERENZ, Jürgen EILS, Hans-Jörg WARNATZ, Thomas RISCH, Marie-Laure YASPO, Ursula D. WEBER, Cynthia C. BARTHOLOMAE, Christof von KALLE, Eszter TURÁNYI, Peter HAUSER, Emma SANDEN, Anna DARABI, Peter SIESJÖ, Jaroslav ŠTĚRBA, Karel ZITTERBART, David SUMERAUER, Peter van SLUIS, Rogier VERSTEEG, Richard VOLCKMANN, Jan KOSTER, Martin U. SCHUHMANN, Martin EBINGER, H. Leighton GRIMES, Giles W. ROBINSON, Amar GAJJAR, Martin MYNAREK, Katja von HOFF, Stefan RUTKOWSKI, Torsten PIETSCH, Wolfram SCHEURLEN, Jörg FELSBERG, Guido REIFENBERGER, Andreas E. KULOZIK, Andreas von DEIMLING, Olaf WITT, Roland EILS, Richard J. GILBERTSON, Andrey KORSHUNOV, Michael D. TAYLOR, Peter LICHTER, Jan O. KORBEL, Robert J. WECHSLER-REYA and Stefan M. PFISTER. Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. Nature. LONDON: NATURE PUBLISHING GROUP, 2014, vol. 511, No 7510, p. "428"-"+", 19 pp. ISSN 0028-0836. Available from: https://dx.doi.org/10.1038/nature13379.
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Basic information
Original name Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma
Authors NORTHCOTT, Paul A. (276 Germany), Catherine LEE (840 United States of America), Thomas ZICHNER (276 Germany), Adrian M. STÜTZ (276 Germany), Serap ERKEK (276 Germany), Daisuke KAWAUCHI (276 Germany), David J.H. SHIH (124 Canada), Volker HOVESTADT (276 Germany), Marc ZAPATKA (276 Germany), Dominik STURM (276 Germany), David T.W. JONES (276 Germany), Marcel KOOL (276 Germany), Marc REMKE (124 Canada), Florence M.G. CAVALLI (124 Canada), Scott ZUYDERDUYN (124 Canada), Gary D. BADER (124 Canada), Scott VANDENBERG (840 United States of America), Lourdes Adriana ESPARZA (840 United States of America), Marina RYZHOVA (643 Russian Federation), Wei WANG (276 Germany), Andrea WITTMANN (276 Germany), Sebastian STARK (276 Germany), Laura SIEBER (276 Germany), Huriye SEKER-CIN (276 Germany), Linda LINKE (203 Czech Republic), Fabian KRATOCHWIL (276 Germany), Natalie JÄGER (276 Germany), Ivo BUCHHALTER (276 Germany), Charles D. IMBUSCH (276 Germany), Gideon ZIPPRICH (276 Germany), Benjamin RAEDER (276 Germany), Sabine SCHMIDT (276 Germany), Nicolle DIESSL (276 Germany), Stephan WOLF (276 Germany), Stefan WIEMANN (276 Germany), Benedikt BRORS (276 Germany), Chris LAWERENZ (276 Germany), Jürgen EILS (276 Germany), Hans-Jörg WARNATZ (276 Germany), Thomas RISCH (276 Germany), Marie-Laure YASPO (276 Germany), Ursula D. WEBER (276 Germany), Cynthia C. BARTHOLOMAE (276 Germany), Christof von KALLE (276 Germany), Eszter TURÁNYI (348 Hungary), Peter HAUSER (348 Hungary), Emma SANDEN (752 Sweden), Anna DARABI (752 Sweden), Peter SIESJÖ (752 Sweden), Jaroslav ŠTĚRBA (203 Czech Republic, guarantor, belonging to the institution), Karel ZITTERBART (203 Czech Republic, belonging to the institution), David SUMERAUER (203 Czech Republic), Peter van SLUIS (528 Netherlands), Rogier VERSTEEG (528 Netherlands), Richard VOLCKMANN (528 Netherlands), Jan KOSTER (528 Netherlands), Martin U. SCHUHMANN (276 Germany), Martin EBINGER (276 Germany), H. Leighton GRIMES (840 United States of America), Giles W. ROBINSON (840 United States of America), Amar GAJJAR (840 United States of America), Martin MYNAREK (276 Germany), Katja von HOFF (276 Germany), Stefan RUTKOWSKI (276 Germany), Torsten PIETSCH (276 Germany), Wolfram SCHEURLEN (276 Germany), Jörg FELSBERG (276 Germany), Guido REIFENBERGER (276 Germany), Andreas E. KULOZIK (276 Germany), Andreas von DEIMLING (276 Germany), Olaf WITT (276 Germany), Roland EILS (276 Germany), Richard J. GILBERTSON (276 Germany), Andrey KORSHUNOV (276 Germany), Michael D. TAYLOR (124 Canada), Peter LICHTER (276 Germany), Jan O. KORBEL (826 United Kingdom of Great Britain and Northern Ireland), Robert J. WECHSLER-REYA (840 United States of America) and Stefan M. PFISTER (276 Germany).
Edition Nature, LONDON, NATURE PUBLISHING GROUP, 2014, 0028-0836.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 30200 3.2 Clinical medicine
Country of publisher United Kingdom of Great Britain and Northern Ireland
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 41.456
RIV identification code RIV/00216224:14110/14:00076119
Organization unit Faculty of Medicine
Doi http://dx.doi.org/10.1038/nature13379
UT WoS 000339335700038
Keywords in English ZINC-FINGER PROTEIN; T-CELL LYMPHOMAGENESIS; STEM-CELLS; SUPER-ENHANCERS; CANCER; MUTATIONS; GENOME; GENE; MYC; SUBGROUP
Tags EL OK
Tags International impact, Reviewed
Changed by Changed by: Soňa Böhmová, učo 232884. Changed: 24/4/2015 13:13.
Abstract
Medulloblastoma 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.
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