Comprehensive Analysis of Chromatin States in Atypical Teratoid/Rhabdoid Tumor Identifies Diverging Roles for SWI/SNF and Polycomb in Gene Regulation

被引：70

作者：

Erkek, Serap ^{[1
,2
,3
,4
,5
]}

Johann, Pascal D. ^{[1
,2
,3
,6
]}

Finetti, Martina A. ^{[7
]}

Drosos, Yiannis ^{[8
]}

Chou, Hsien-Chao ^{[8
]}

Zapatka, Marc ^{[9
,10
]}

Sturm, Dominik ^{[1
,2
,3
,6
]}

Jones, David T. W. ^{[1
,2
,3
]}

Korshunov, Andrey ^{[11
,12
]}

Rhyzova, Marina ^{[13
]}

Wolf, Stephan ^{[14
]}

Mallm, Jan-Philipp ^{[15
,16
]}

Beck, Katja ^{[16
]}

Witt, Olaf ^{[6
,17
]}

Kulozik, Andreas E. ^{[6
]}

Fruehwald, Michael C. ^{[18
,19
]}

Northcott, Paul A. ^{[1
,2
,3
,20
]}

Korbel, Jan O. ^{[4
]}

Lichter, Peter ^{[9
,10
,16
]}

Eils, Roland ^{[15
,21
]}

Gajjar, Amar ^{[8
]}

Roberts, Charles W. M. ^{[8
]}

Williamson, Daniel ^{[7
]}

Hasselblatt, Martin ^{[22
]}

Chavez, Lukas ^{[1
,2
,3
]}

Pfister, Stefan M. ^{[1
,2
,3
,6
]}

Kool, Marcel ^{[1
,2
,3
]}

机构：

[1] NCT Heidelberg KiTZ, Hopp Childrens Canc Ctr, D-69120 Heidelberg, Germany

[2] German Canc Res Ctr, Div Pediat Neurooncol, Neuenheimer Feld 280, D-69120 Heidelberg, Germany

[3] German Canc Consortium DKTK, Neuenheimer Feld 280, D-69120 Heidelberg, Germany

[4] European Mol Biol Lab, Genome Biol Unit, D-69117 Heidelberg, Germany

[5] Izmir Biomed & Genome Ctr, TR-35340 Izmir, Turkey

[6] Univ Hosp Heidelberg, Dept Pediat Hematol & Oncol, D-69120 Heidelberg, Germany

[7] Newcastle Univ, Wolfson Childhood Canc Res Ctr, Northern Inst Canc Res, Newcastle Upon Tyne NE2, Tyne & Wear, England

[8] St Jude Childrens Res Hosp, Dept Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA

[9] German Canc Res Ctr, Div Mol Genet, D-69120 Heidelberg, Germany

[10] German Canc Consortium DKTK, D-69120 Heidelberg, Germany

[11] Univ Hosp Heidelberg, Dept Neuropathol, D-69120 Heidelberg, Germany

[12] German Canc Res Ctr, Clin Cooperat Unit Neuropathol, D-69120 Heidelberg, Germany

[13] Burdenko Neurosurg Inst, Dept Neuropathol, Moscow 125047, Russia

[14] German Canc Res Ctr, Genom & Prote Core Facil, D-69120 Heidelberg, Germany

[15] German Canc Res Ctr, Genome Org & Funct Res Grp, D-69120 Heidelberg, Germany

[16] DKFZ, Heidelberg Ctr Personalized Oncol, DKFZ HIPO, D-69120 Heidelberg, Germany

[17] German Canc Res Ctr, Clin Cooperat Unit Pediat Oncol, D-69120 Heidelberg, Germany

[18] Univ Childrens Hosp Augsburg, Swabian Childrens Canc Ctr, D-86156 Augsburg, Germany

[19] EU RHAB Registry Ctr, D-86156 Augsburg, Germany

[20] St Jude Childrens Res Hosp, Dept Dev Neurobiol, 332 N Lauderdale St, Memphis, TN 38105 USA

[21] German Canc Res Ctr, Div Theoret Bioinformat, D-69120 Heidelberg, Germany

[22] Univ Hosp Munster, Inst Neuropathol, D-48149 Munster, Germany

来源：

CANCER CELL | 2019年 / 35卷 / 01期

关键词：

MALIGNANT RHABDOID TUMORS; TRANSCRIPTION FACTORS; EXPRESSION; COMPLEXES; EPIGENOME; EZH2; CNS; ANNOTATION; INHIBITION; ELEMENTS;

D O I：

10.1016/j.ccell.2018.11.014

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Biallelic inactivation of SMARCB1, encoding amember of the SWI/SNF chromatin remodeling complex, is the hallmark genetic aberration of atypical teratoid rhabdoid tumors (ATRT). Here, we report how loss of SMARCB1 affects the epigenome in these tumors. Using chromatin immunoprecipitation sequencing (ChIP-seq) on primary tumors for a series of active and repressive histone marks, we identified the chromatin states differentially represented in ATRTs compared with other brain tumors and non-neoplastic brain. Re-expression of SMARCB1 in ATRT cell lines enabled confirmation of our genome-wide findings for the chromatin states. Additional generation of ChIP-seq data for SWI/SNF and Polycomb group proteins and the transcriptional repressor protein REST determined differential dependencies of SWI/SNF and Polycomb complexes in regulation of diverse gene sets in ATRTs.

引用

页码：95 / +

页数：24

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