Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes

被引：424

作者：

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

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

Zapatka, Marc ^{[2
,5
]}

Kerl, Kornelius ^{[6
]}

Buchhalter, Ivo ^{[7
]}

Hovestadt, Volker ^{[2
,5
]}

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

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

Hermann, Carl ^{[7
]}

Wang, Maia Segura ^{[4
]}

Korshunov, Andrey ^{[8
,9
]}

Rhyzova, Marina ^{[10
]}

Groebner, Susanne ^{[1
,11
]}

Brabetz, Sebastian ^{[1
]}

Chavez, Lukas ^{[1
]}

Bens, Susanne ^{[11
]}

Groeschel, Stefan ^{[12
]}

Kratochwil, Fabian ^{[1
,2
]}

Wittmann, Andrea ^{[1
,2
]}

Sieber, Laura ^{[1
,2
]}

Geoerg, Christina ^{[12
]}

Wolf, Stefan ^{[13
]}

Beck, Katja ^{[2
,5
]}

Oyen, Florian ^{[14
]}

Capper, David ^{[8
,9
]}

van Sluis, Peter ^{[15
]}

Volckmann, Richard ^{[15
]}

Koster, Jan ^{[15
]}

Versteeg, Rogier ^{[15
]}

von Deimling, Andreas ^{[8
,9
]}

Milde, Till ^{[3
,16
]}

Witt, Olaf ^{[3
,16
]}

Kulozik, Andreas E. ^{[3
]}

Ebinger, Martin ^{[17
]}

Shalaby, Tarek ^{[18
]}

Grotzer, Michael ^{[18
]}

Sumerauer, David ^{[19
,20
]}

Zamecnik, Josef ^{[21
]}

Mora, Jaume ^{[22
]}

Jabado, Nada ^{[23
,24
]}

Taylor, Michael D. ^{[25
]}

Huang, Annie ^{[25
]}

Aronica, Eleonora ^{[26
]}

Bertoni, Anna ^{[5
]}

Radlwimmer, Bernhard ^{[5
]}

Pietsch, Torsten ^{[27
]}

Schueller, Ulrich ^{[28
]}

Schneppenheim, Reinhard ^{[14
]}

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

Korbel, Jan O. ^{[4
]}

机构：

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

[2] German Canc Res Ctr, Core Ctr Heidelberg, D-69120 Heidelberg, Germany

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

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

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

[6] Univ Childrens Hosp Muenster, Dept Pediat Hematol & Oncol, D-48149 Munster, Germany

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

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

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

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

[11] Inst Human Genet, D-24105 Kiel, Germany

[12] Natl Ctr Tumorerkrankungen, Div Translat Oncol, D-69120 Heidelberg, Germany

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

[14] Univ Hosp Hamburg Eppendorf, Dept Pediat Hematol & Oncol, D-20246 Hamburg, Germany

[15] Univ Amsterdam, Acad Med Ctr, Dept Oncogen, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands

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

[17] Univ Tubingen, Dept Gen Pediat Hematol & Oncol, D-72076 Tubingen, Germany

[18] Univ Childrens Hosp, Childrens Res Ctr, Dept Neurooncol, CH-8032 Zurich, Switzerland

[19] Charles Univ Prague, Dept Pediat Hematol & Oncol, Prague 15006, Czech Republic

[20] Univ Hosp Motol, Prague 15006, Czech Republic

[21] Charles Univ Prague, Univ Hosp Motol, Fac Med 2, Dept Pathol & Mol Med, Prague 15006, Czech Republic

[22] Hosp San Joan de Deu, Childrens Hosp, Dept Hematol & Oncol, Barcelona 08950, Spain

[23] McGill Univ, Ctr Hlth, Res Inst, Dept Pediat, Montreal, PQ H3A 1A4, Canada

[24] McGill Univ, Ctr Hlth, Res Inst, Dept Human Genet, Montreal, PQ H3A 1A4, Canada

[25] Univ Toronto, Hosp Sick Children, Arthur & Sonia Labatt Brain Tumor Res Ctr, Toronto, ON M5G 0A4, Canada

[26] Acad Med Ctr, Dept Neuropathol, Amsterdam, Netherlands

[27] Univ Bonn, Dept Neuropathol, D-53127 Bonn, Germany

[28] Univ Munich, Ctr Neuropathol, Marchioninistr 15, D-81377 Munich, Germany

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

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

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

[32] St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA

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

来源：

CANCER CELL | 2016年 / 29卷 / 03期

关键词：

TERATOID RHABDOID TUMORS; MUTATIONS; CHILDREN; THERAPY; EXPRESSION; SURVIVAL; ABSENCE; ATRT; MAP;

D O I：

10.1016/j.ccell.2016.02.001

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed 192 ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets.

引用

页码：379 / 393

页数：15

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