Enhancer hijacking activates GFI1 family oncogenes in
medulloblastoma

J 2014

Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma

NORTHCOTT, Paul A., Catherine LEE, Thomas ZICHNER, Adrian M. STÜTZ, Serap ERKEK et. al.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

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

Abstract

V originále

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.

Citovat

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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   author = {Northcott, Paul A. and Lee, Catherine and Zichner, Thomas and Stütz, Adrian M. and Erkek, Serap and Kawauchi, Daisuke and Shih, David J.H. and Hovestadt, Volker and Zapatka, Marc and Sturm, Dominik and Jones, David T.W. and Kool, Marcel and Remke, Marc and Cavalli, Florence M.G. and Zuyderduyn, Scott and Bader, Gary D. and VandenBerg, Scott and Esparza, Lourdes Adriana and Ryzhova, Marina and Wang, Wei and Wittmann, Andrea and Stark, Sebastian and Sieber, Laura and SekerandCin, Huriye and Linke, Linda and Kratochwil, Fabian and Jäger, Natalie and Buchhalter, Ivo and Imbusch, Charles D. and Zipprich, Gideon and Raeder, Benjamin and Schmidt, Sabine and Diessl, Nicolle and Wolf, Stephan and Wiemann, Stefan and Brors, Benedikt and Lawerenz, Chris and Eils, Jürgen and Warnatz, HansandJörg and Risch, Thomas and Yaspo, MarieandLaure and Weber, Ursula D. and Bartholomae, Cynthia C. and Kalle, Christof von and Turányi, Eszter and Hauser, Peter and Sanden, Emma and Darabi, Anna and Siesjö, Peter and Štěrba, Jaroslav and Zitterbart, Karel and Sumerauer, David and Sluis, Peter van and Versteeg, Rogier and Volckmann, Richard and Koster, Jan and Schuhmann, Martin U. and Ebinger, Martin and Grimes, H. Leighton and Robinson, Giles W. and Gajjar, Amar and Mynarek, Martin and Hoff, Katja von and Rutkowski, Stefan and Pietsch, Torsten and Scheurlen, Wolfram and Felsberg, Jörg and Reifenberger, Guido and Kulozik, Andreas E. and Deimling, Andreas von and Witt, Olaf and Eils, Roland and Gilbertson, Richard J. and Korshunov, Andrey and Taylor, Michael D. and Lichter, Peter and Korbel, Jan O. and WechslerandReya, Robert J. and Pfister, Stefan M.},
   article_location = {LONDON},
   article_number = {7510},
   doi = {http://dx.doi.org/10.1038/nature13379},
   keywords = {ZINC-FINGER PROTEIN; T-CELL LYMPHOMAGENESIS; STEM-CELLS; SUPER-ENHANCERS; CANCER; MUTATIONS; GENOME; GENE; MYC; SUBGROUP},
   language = {eng},
   issn = {0028-0836},
   journal = {Nature},
   title = {Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma},
   volume = {511},
   year = {2014}
}

TY  - JOUR
ID  - 1194769
AU  - Northcott, Paul A. - Lee, Catherine - Zichner, Thomas - Stütz, Adrian M. - Erkek, Serap - Kawauchi, Daisuke - Shih, David J.H. - Hovestadt, Volker - Zapatka, Marc - Sturm, Dominik - Jones, David T.W. - Kool, Marcel - Remke, Marc - Cavalli, Florence M.G. - Zuyderduyn, Scott - Bader, Gary D. - VandenBerg, Scott - Esparza, Lourdes Adriana - Ryzhova, Marina - Wang, Wei - Wittmann, Andrea - Stark, Sebastian - Sieber, Laura - Seker-Cin, Huriye - Linke, Linda - Kratochwil, Fabian - Jäger, Natalie - Buchhalter, Ivo - Imbusch, Charles D. - Zipprich, Gideon - Raeder, Benjamin - Schmidt, Sabine - Diessl, Nicolle - Wolf, Stephan - Wiemann, Stefan - Brors, Benedikt - Lawerenz, Chris - Eils, Jürgen - Warnatz, Hans-Jörg - Risch, Thomas - Yaspo, Marie-Laure - Weber, Ursula D. - Bartholomae, Cynthia C. - Kalle, Christof von - Turányi, Eszter - Hauser, Peter - Sanden, Emma - Darabi, Anna - Siesjö, Peter - Štěrba, Jaroslav - Zitterbart, Karel - Sumerauer, David - Sluis, Peter van - Versteeg, Rogier - Volckmann, Richard - Koster, Jan - Schuhmann, Martin U. - Ebinger, Martin - Grimes, H. Leighton - Robinson, Giles W. - Gajjar, Amar - Mynarek, Martin - Hoff, Katja von - Rutkowski, Stefan - Pietsch, Torsten - Scheurlen, Wolfram - Felsberg, Jörg - Reifenberger, Guido - Kulozik, Andreas E. - Deimling, Andreas von - Witt, Olaf - Eils, Roland - Gilbertson, Richard J. - Korshunov, Andrey - Taylor, Michael D. - Lichter, Peter - Korbel, Jan O. - Wechsler-Reya, Robert J. - Pfister, Stefan M.
PY  - 2014
TI  - Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma
JF  - Nature
VL  - 511
IS  - 7510
SP  - "428"-"+"
EP  - "428"-"+"
PB  - NATURE PUBLISHING GROUP
SN  - 00280836
KW  - ZINC-FINGER PROTEIN
KW  - T-CELL LYMPHOMAGENESIS
KW  - STEM-CELLS
KW  - SUPER-ENHANCERS
KW  - CANCER
KW  - MUTATIONS
KW  - GENOME
KW  - GENE
KW  - MYC
KW  - SUBGROUP
N2  - 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.
ER  -

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. \textit{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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