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Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma

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Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. / 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; von Kalle, Christof; Turányi, Eszter; Hauser, Peter; Sanden, Emma; Darabi, Anna; Siesjö, Peter; Sterba, Jaroslav; Zitterbart, Karel; Sumerauer, David; van Sluis, Peter; Versteeg, Rogier; Volckmann, Richard; Koster, Jan; Schuhmann, Martin U; Ebinger, Martin; Grimes, H Leighton; Robinson, Giles W; Gajjar, Amar; Mynarek, Martin; von Hoff, Katja; Rutkowski, Stefan; Pietsch, Torsten; Scheurlen, Wolfram; Felsberg, Jörg; Reifenberger, Guido; Kulozik, Andreas E; von Deimling, Andreas; Witt, Olaf; Eils, Roland; Gilbertson, Richard J; Korshunov, Andrey; Taylor, Michael D; Lichter, Peter; Korbel, Jan O; Wechsler-Reya, Robert J; Pfister, Stefan M.

In: NATURE, Vol. 511, No. 7510, 24.07.2014, p. 428-434.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Northcott, PA, Lee, C, Zichner, T, Stütz, AM, Erkek, S, Kawauchi, D, Shih, DJH, Hovestadt, V, Zapatka, M, Sturm, D, Jones, DTW, Kool, M, Remke, M, Cavalli, FMG, Zuyderduyn, S, Bader, GD, VandenBerg, S, Esparza, LA, Ryzhova, M, Wang, W, Wittmann, A, Stark, S, Sieber, L, Seker-Cin, H, Linke, L, Kratochwil, F, Jäger, N, Buchhalter, I, Imbusch, CD, Zipprich, G, Raeder, B, Schmidt, S, Diessl, N, Wolf, S, Wiemann, S, Brors, B, Lawerenz, C, Eils, J, Warnatz, H-J, Risch, T, Yaspo, M-L, Weber, UD, Bartholomae, CC, von Kalle, C, Turányi, E, Hauser, P, Sanden, E, Darabi, A, Siesjö, P, Sterba, J, Zitterbart, K, Sumerauer, D, van Sluis, P, Versteeg, R, Volckmann, R, Koster, J, Schuhmann, MU, Ebinger, M, Grimes, HL, Robinson, GW, Gajjar, A, Mynarek, M, von Hoff, K, Rutkowski, S, Pietsch, T, Scheurlen, W, Felsberg, J, Reifenberger, G, Kulozik, AE, von Deimling, A, Witt, O, Eils, R, Gilbertson, RJ, Korshunov, A, Taylor, MD, Lichter, P, Korbel, JO, Wechsler-Reya, RJ & Pfister, SM 2014, 'Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma', NATURE, vol. 511, no. 7510, pp. 428-434. https://doi.org/10.1038/nature13379

APA

Northcott, P. A., Lee, C., Zichner, T., Stütz, A. M., Erkek, S., Kawauchi, D., Shih, D. J. H., Hovestadt, V., Zapatka, M., Sturm, D., Jones, D. T. W., Kool, M., Remke, M., Cavalli, F. M. G., Zuyderduyn, S., Bader, G. D., VandenBerg, S., Esparza, L. A., Ryzhova, M., ... Pfister, S. M. (2014). Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. NATURE, 511(7510), 428-434. https://doi.org/10.1038/nature13379

Vancouver

Northcott PA, Lee C, Zichner T, Stütz AM, Erkek S, Kawauchi D et al. Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. NATURE. 2014 Jul 24;511(7510):428-434. https://doi.org/10.1038/nature13379

Bibtex

@article{24ac830552134f21bf5716b869f94cbd,
title = "Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma",
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.",
keywords = "Animals, Child, Chromosomes, Human, Pair 9, DNA-Binding Proteins, Enhancer Elements, Genetic, Genomic Structural Variation, Humans, Medulloblastoma, Mice, Oncogenes, Proto-Oncogene Proteins, Repressor Proteins, Transcription Factors",
author = "Northcott, {Paul A} and Catherine Lee and Thomas Zichner and St{\"u}tz, {Adrian M} and Serap Erkek and Daisuke Kawauchi and Shih, {David J H} and Volker Hovestadt and Marc Zapatka and Dominik Sturm and Jones, {David T W} and Marcel Kool and Marc Remke and Cavalli, {Florence M G} and Scott Zuyderduyn and Bader, {Gary D} and Scott VandenBerg and Esparza, {Lourdes Adriana} and Marina Ryzhova and Wei Wang and Andrea Wittmann and Sebastian Stark and Laura Sieber and Huriye Seker-Cin and Linda Linke and Fabian Kratochwil and Natalie J{\"a}ger and Ivo Buchhalter and Imbusch, {Charles D} and Gideon Zipprich and Benjamin Raeder and Sabine Schmidt and Nicolle Diessl and Stephan Wolf and Stefan Wiemann and Benedikt Brors and Chris Lawerenz and J{\"u}rgen Eils and Hans-J{\"o}rg Warnatz and Thomas Risch and Marie-Laure Yaspo and Weber, {Ursula D} and Bartholomae, {Cynthia C} and {von Kalle}, Christof and Eszter Tur{\'a}nyi and Peter Hauser and Emma Sanden and Anna Darabi and Peter Siesj{\"o} and Jaroslav Sterba and Karel Zitterbart and David Sumerauer and {van Sluis}, Peter and Rogier Versteeg and Richard Volckmann and Jan Koster and Schuhmann, {Martin U} and Martin Ebinger and Grimes, {H Leighton} and Robinson, {Giles W} and Amar Gajjar and Martin Mynarek and {von Hoff}, Katja and Stefan Rutkowski and Torsten Pietsch and Wolfram Scheurlen and J{\"o}rg Felsberg and Guido Reifenberger and Kulozik, {Andreas E} and {von Deimling}, Andreas and Olaf Witt and Roland Eils and Gilbertson, {Richard J} and Andrey Korshunov and Taylor, {Michael D} and Peter Lichter and Korbel, {Jan O} and Wechsler-Reya, {Robert J} and Pfister, {Stefan M}",
year = "2014",
month = jul,
day = "24",
doi = "10.1038/nature13379",
language = "English",
volume = "511",
pages = "428--434",
journal = "NATURE",
issn = "0028-0836",
publisher = "NATURE PUBLISHING GROUP",
number = "7510",

}

RIS

TY - JOUR

T1 - Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma

AU - Northcott, Paul A

AU - Lee, Catherine

AU - Zichner, Thomas

AU - Stütz, Adrian M

AU - Erkek, Serap

AU - Kawauchi, Daisuke

AU - Shih, David J H

AU - Hovestadt, Volker

AU - Zapatka, Marc

AU - Sturm, Dominik

AU - Jones, David T W

AU - Kool, Marcel

AU - Remke, Marc

AU - Cavalli, Florence M G

AU - Zuyderduyn, Scott

AU - Bader, Gary D

AU - VandenBerg, Scott

AU - Esparza, Lourdes Adriana

AU - Ryzhova, Marina

AU - Wang, Wei

AU - Wittmann, Andrea

AU - Stark, Sebastian

AU - Sieber, Laura

AU - Seker-Cin, Huriye

AU - Linke, Linda

AU - Kratochwil, Fabian

AU - Jäger, Natalie

AU - Buchhalter, Ivo

AU - Imbusch, Charles D

AU - Zipprich, Gideon

AU - Raeder, Benjamin

AU - Schmidt, Sabine

AU - Diessl, Nicolle

AU - Wolf, Stephan

AU - Wiemann, Stefan

AU - Brors, Benedikt

AU - Lawerenz, Chris

AU - Eils, Jürgen

AU - Warnatz, Hans-Jörg

AU - Risch, Thomas

AU - Yaspo, Marie-Laure

AU - Weber, Ursula D

AU - Bartholomae, Cynthia C

AU - von Kalle, Christof

AU - Turányi, Eszter

AU - Hauser, Peter

AU - Sanden, Emma

AU - Darabi, Anna

AU - Siesjö, Peter

AU - Sterba, Jaroslav

AU - Zitterbart, Karel

AU - Sumerauer, David

AU - van Sluis, Peter

AU - Versteeg, Rogier

AU - Volckmann, Richard

AU - Koster, Jan

AU - Schuhmann, Martin U

AU - Ebinger, Martin

AU - Grimes, H Leighton

AU - Robinson, Giles W

AU - Gajjar, Amar

AU - Mynarek, Martin

AU - von Hoff, Katja

AU - Rutkowski, Stefan

AU - Pietsch, Torsten

AU - Scheurlen, Wolfram

AU - Felsberg, Jörg

AU - Reifenberger, Guido

AU - Kulozik, Andreas E

AU - von Deimling, Andreas

AU - Witt, Olaf

AU - Eils, Roland

AU - Gilbertson, Richard J

AU - Korshunov, Andrey

AU - Taylor, Michael D

AU - Lichter, Peter

AU - Korbel, Jan O

AU - Wechsler-Reya, Robert J

AU - Pfister, Stefan M

PY - 2014/7/24

Y1 - 2014/7/24

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.

AB - 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.

KW - Animals

KW - Child

KW - Chromosomes, Human, Pair 9

KW - DNA-Binding Proteins

KW - Enhancer Elements, Genetic

KW - Genomic Structural Variation

KW - Humans

KW - Medulloblastoma

KW - Mice

KW - Oncogenes

KW - Proto-Oncogene Proteins

KW - Repressor Proteins

KW - Transcription Factors

U2 - 10.1038/nature13379

DO - 10.1038/nature13379

M3 - SCORING: Journal article

C2 - 25043047

VL - 511

SP - 428

EP - 434

JO - NATURE

JF - NATURE

SN - 0028-0836

IS - 7510

ER -