Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas

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Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas. / Bender, Sebastian; Tang, Yujie; Lindroth, Anders M; Hovestadt, Volker; Jones, David T W; Kool, Marcel; Zapatka, Marc; Northcott, Paul A; Sturm, Dominik; Wang, Wei Guo; Radlwimmer, Bernhard; Højfeldt, Jonas W; Truffaux, Nathalène; Castel, David; Schubert, Simone; Ryzhova, Marina; Seker-Cin, Huriye; Gronych, Jan; Johann, Pascal David; Stark, Sebastian; Meyer, Jochen; Milde, Till; Schuhmann, Martin; Ebinger, Martin; Monoranu, Camelia-Maria; Ponnuswami, Anitha; Chen, Spenser; Jones, Chris; Witt, Olaf; Collins, V Peter; von Deimling, Andreas; Jabado, Nada; Puget, Stephanie; Grill, Jacques; Helin, Kristian; Korshunov, Andrey; Lichter, Peter; Monje, Michelle; Plass, Christoph; Cho, Yoon-Jae; Pfister, Stefan M.

In: Cancer Cell, Vol. 24, No. 5, 11.11.2013, p. 660-72.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Bender, S, Tang, Y, Lindroth, AM, Hovestadt, V, Jones, DTW, Kool, M, Zapatka, M, Northcott, PA, Sturm, D, Wang, WG, Radlwimmer, B, Højfeldt, JW, Truffaux, N, Castel, D, Schubert, S, Ryzhova, M, Seker-Cin, H, Gronych, J, Johann, PD, Stark, S, Meyer, J, Milde, T, Schuhmann, M, Ebinger, M, Monoranu, C-M, Ponnuswami, A, Chen, S, Jones, C, Witt, O, Collins, VP, von Deimling, A, Jabado, N, Puget, S, Grill, J, Helin, K, Korshunov, A, Lichter, P, Monje, M, Plass, C, Cho, Y-J & Pfister, SM 2013, 'Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas', Cancer Cell, vol. 24, no. 5, pp. 660-72. https://doi.org/10.1016/j.ccr.2013.10.006

APA

Bender, S., Tang, Y., Lindroth, A. M., Hovestadt, V., Jones, D. T. W., Kool, M., Zapatka, M., Northcott, P. A., Sturm, D., Wang, W. G., Radlwimmer, B., Højfeldt, J. W., Truffaux, N., Castel, D., Schubert, S., Ryzhova, M., Seker-Cin, H., Gronych, J., Johann, P. D., ... Pfister, S. M. (2013). Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas. Cancer Cell, 24(5), 660-72. https://doi.org/10.1016/j.ccr.2013.10.006

Vancouver

Bender S, Tang Y, Lindroth AM, Hovestadt V, Jones DTW, Kool M et al. Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas. Cancer Cell. 2013 Nov 11;24(5):660-72. https://doi.org/10.1016/j.ccr.2013.10.006

Author

Bender, Sebastian ; Tang, Yujie ; Lindroth, Anders M ; Hovestadt, Volker ; Jones, David T W ; Kool, Marcel ; Zapatka, Marc ; Northcott, Paul A ; Sturm, Dominik ; Wang, Wei Guo ; Radlwimmer, Bernhard ; Højfeldt, Jonas W ; Truffaux, Nathalène ; Castel, David ; Schubert, Simone ; Ryzhova, Marina ; Seker-Cin, Huriye ; Gronych, Jan ; Johann, Pascal David ; Stark, Sebastian ; Meyer, Jochen ; Milde, Till ; Schuhmann, Martin ; Ebinger, Martin ; Monoranu, Camelia-Maria ; Ponnuswami, Anitha ; Chen, Spenser ; Jones, Chris ; Witt, Olaf ; Collins, V Peter ; von Deimling, Andreas ; Jabado, Nada ; Puget, Stephanie ; Grill, Jacques ; Helin, Kristian ; Korshunov, Andrey ; Lichter, Peter ; Monje, Michelle ; Plass, Christoph ; Cho, Yoon-Jae ; Pfister, Stefan M. / Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas. In: Cancer Cell. 2013 ; Vol. 24, No. 5. pp. 660-72.

Bibtex

@article{b3f5cab317d14c5899d4e8678dbea1df,
title = "Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas",
abstract = "Two recurrent mutations, K27M and G34R/V, within histone variant H3.3 were recently identified in ∼50% of pHGGs. Both mutations define clinically and biologically distinct subgroups of pHGGs. Here, we provide further insight about the dominant-negative effect of K27M mutant H3.3, leading to a global reduction of the repressive histone mark H3K27me3. We demonstrate that this is caused by aberrant recruitment of the PRC2 complex to K27M mutant H3.3 and enzymatic inhibition of the H3K27me3-establishing methyltransferase EZH2. By performing chromatin immunoprecipitation followed by next-generation sequencing and whole-genome bisulfite sequencing in primary pHGGs, we show that reduced H3K27me3 levels and DNA hypomethylation act in concert to activate gene expression in K27M mutant pHGGs.",
author = "Sebastian Bender and Yujie Tang and Lindroth, {Anders M} and Volker Hovestadt and Jones, {David T W} and Marcel Kool and Marc Zapatka and Northcott, {Paul A} and Dominik Sturm and Wang, {Wei Guo} and Bernhard Radlwimmer and H{\o}jfeldt, {Jonas W} and Nathal{\`e}ne Truffaux and David Castel and Simone Schubert and Marina Ryzhova and Huriye Seker-Cin and Jan Gronych and Johann, {Pascal David} and Sebastian Stark and Jochen Meyer and Till Milde and Martin Schuhmann and Martin Ebinger and Camelia-Maria Monoranu and Anitha Ponnuswami and Spenser Chen and Chris Jones and Olaf Witt and Collins, {V Peter} and {von Deimling}, Andreas and Nada Jabado and Stephanie Puget and Jacques Grill and Kristian Helin and Andrey Korshunov and Peter Lichter and Michelle Monje and Christoph Plass and Yoon-Jae Cho and Pfister, {Stefan M}",
note = "Copyright {\textcopyright} 2013 Elsevier Inc. All rights reserved.",
year = "2013",
month = nov,
day = "11",
doi = "10.1016/j.ccr.2013.10.006",
language = "English",
volume = "24",
pages = "660--72",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "5",

}

RIS

TY - JOUR

T1 - Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas

AU - Bender, Sebastian

AU - Tang, Yujie

AU - Lindroth, Anders M

AU - Hovestadt, Volker

AU - Jones, David T W

AU - Kool, Marcel

AU - Zapatka, Marc

AU - Northcott, Paul A

AU - Sturm, Dominik

AU - Wang, Wei Guo

AU - Radlwimmer, Bernhard

AU - Højfeldt, Jonas W

AU - Truffaux, Nathalène

AU - Castel, David

AU - Schubert, Simone

AU - Ryzhova, Marina

AU - Seker-Cin, Huriye

AU - Gronych, Jan

AU - Johann, Pascal David

AU - Stark, Sebastian

AU - Meyer, Jochen

AU - Milde, Till

AU - Schuhmann, Martin

AU - Ebinger, Martin

AU - Monoranu, Camelia-Maria

AU - Ponnuswami, Anitha

AU - Chen, Spenser

AU - Jones, Chris

AU - Witt, Olaf

AU - Collins, V Peter

AU - von Deimling, Andreas

AU - Jabado, Nada

AU - Puget, Stephanie

AU - Grill, Jacques

AU - Helin, Kristian

AU - Korshunov, Andrey

AU - Lichter, Peter

AU - Monje, Michelle

AU - Plass, Christoph

AU - Cho, Yoon-Jae

AU - Pfister, Stefan M

N1 - Copyright © 2013 Elsevier Inc. All rights reserved.

PY - 2013/11/11

Y1 - 2013/11/11

N2 - Two recurrent mutations, K27M and G34R/V, within histone variant H3.3 were recently identified in ∼50% of pHGGs. Both mutations define clinically and biologically distinct subgroups of pHGGs. Here, we provide further insight about the dominant-negative effect of K27M mutant H3.3, leading to a global reduction of the repressive histone mark H3K27me3. We demonstrate that this is caused by aberrant recruitment of the PRC2 complex to K27M mutant H3.3 and enzymatic inhibition of the H3K27me3-establishing methyltransferase EZH2. By performing chromatin immunoprecipitation followed by next-generation sequencing and whole-genome bisulfite sequencing in primary pHGGs, we show that reduced H3K27me3 levels and DNA hypomethylation act in concert to activate gene expression in K27M mutant pHGGs.

AB - Two recurrent mutations, K27M and G34R/V, within histone variant H3.3 were recently identified in ∼50% of pHGGs. Both mutations define clinically and biologically distinct subgroups of pHGGs. Here, we provide further insight about the dominant-negative effect of K27M mutant H3.3, leading to a global reduction of the repressive histone mark H3K27me3. We demonstrate that this is caused by aberrant recruitment of the PRC2 complex to K27M mutant H3.3 and enzymatic inhibition of the H3K27me3-establishing methyltransferase EZH2. By performing chromatin immunoprecipitation followed by next-generation sequencing and whole-genome bisulfite sequencing in primary pHGGs, we show that reduced H3K27me3 levels and DNA hypomethylation act in concert to activate gene expression in K27M mutant pHGGs.

U2 - 10.1016/j.ccr.2013.10.006

DO - 10.1016/j.ccr.2013.10.006

M3 - Journal article

C2 - 24183680

VL - 24

SP - 660

EP - 672

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 5

ER -

ID: 94394591