Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups

被引：833

作者：

Pajtler, Kristian W. ^{[1
,2
]}

Witt, Hendrik ^{[1
,3
,4
]}

Sill, Martin ^{[5
]}

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

Hovestadt, Volker ^{[6
]}

Kratochwil, Fabian ^{[1
]}

Wani, Khalida ^{[7
]}

Tatevossian, Ruth ^{[8
]}

Punchihewa, Chandanamali ^{[8
]}

Johann, Pascal ^{[1
]}

Reimand, Jueri ^{[9
]}

Warnatz, Hans-Joerg ^{[10
]}

Ryzhova, Marina ^{[11
]}

Mack, Steve ^{[12
]}

Ramaswamy, Vijay ^{[12
,13
]}

Capper, David ^{[14
,15
]}

Schweizer, Leonille ^{[14
,15
]}

Sieber, Laura ^{[1
]}

Wittmann, Andrea ^{[1
]}

Huang, Zhiqin ^{[6
]}

van Sluis, Peter ^{[16
]}

Volckmann, Richard ^{[16
]}

Koster, Jan ^{[16
]}

Versteeg, Rogier ^{[16
]}

Fults, Daniel ^{[17
]}

Toledano, Helen ^{[18
]}

Avigad, Smadar ^{[19
]}

Hoffman, Lindsey M. ^{[20
]}

Donson, Andrew M. ^{[20
]}

Foreman, Nicholas ^{[20
]}

Hewer, Ekkehard ^{[21
]}

Zitterbart, Karel ^{[22
,23
,24
]}

Gilbert, Mark ^{[25
]}

Armstrong, Terri S. ^{[25
,26
]}

Gupta, Nalin ^{[27
]}

Allen, Jeffrey C. ^{[28
,29
]}

Karajannis, Matthias A. ^{[30
,31
]}

Zagzag, David ^{[32
]}

Hasselblatt, Martin ^{[33
]}

Kulozik, Andreas E. ^{[3
]}

Witt, Olaf ^{[3
,34
]}

Collins, V. Peter ^{[35
]}

von Hoff, Katja ^{[36
]}

Rutkowski, Stefan ^{[36
]}

Pietsch, Torsten ^{[37
]}

Bader, Gary ^{[9
]}

Yaspo, Marie-Laure ^{[10
]}

von Deimling, Andreas ^{[14
,15
]}

Lichter, Peter ^{[4
,6
]}

Taylor, Michael D. ^{[12
]}

机构：

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

[2] Univ Childrens Hosp Essen, Dept Pediat Oncol & Hematol, D-45147 Essen, Germany

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

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

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

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

[7] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA

[8] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA

[9] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada

[10] Max Planck Inst Mol Genet, Dept Vertebrate Genom, D-14195 Berlin, Germany

[11] NN Burdenko Inst Neurosurg, Dept Neuropathol, Moscow 125047, Russia

[12] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Div Neurosurg, Toronto, ON M5G 1X8, Canada

[13] Hosp Sick Children, Div Hematol Oncol, Toronto, ON M5G 1X8, Canada

[14] Heidelberg Univ, Dept Neuropathol, D-69120 Heidelberg, Germany

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

[16] Univ Amsterdam, Acad Med Ctr, Dept Oncogen, NL-1105 AZ Amsterdam, Netherlands

[17] Univ Utah, Salt Lake City, UT 84132 USA

[18] Schneider Childrens Med Ctr Israel, Pediat Hematol Oncol, IL-49202 Petah Tiqwa, Israel

[19] Tel Aviv Univ, Schneider Childrens Med Ctr Israel, Dept Mol Oncol, IL-49202 Tel Aviv, Israel

[20] Univ Colorado Denver, Dept Pediat, Aurora, CO 80045 USA

[21] Univ Bern, Dept Pathol, CH-3010 Bern, Switzerland

[22] Univ Hosp Brno, Fac Med, Dept Pediat Oncol, Brno 61300, Czech Republic

[23] Masaryk Univ, Brno 61300, Czech Republic

[24] Masaryk Mem Canc Inst, Reg Ctr Appl Mol Oncol, Brno 65653, Czech Republic

[25] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Div Canc Med, Houston, TX 77030 USA

[26] Univ Texas Hlth Sci Ctr SON, Dept Family Hlth, Houston, TX 77030 USA

[27] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA

[28] NYU, Langone Med Ctr, Dept Pediat, New York, NY 10016 USA

[29] NYU, Langone Med Ctr, Dept Neurol, New York, NY 10016 USA

[30] NYU, Langone Med Ctr, Dept Pediat, Div Pediat Hematol & Oncol, New York, NY 10016 USA

[31] NYU, Langone Med Ctr, Dept Otolaryngol, Div Pediat Hematol & Oncol, New York, NY 10016 USA

[32] NYU, Langone Med Ctr, Dept Pathol, New York, NY 10016 USA

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

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

[35] Univ Cambridge, Dept Pathol, Cambridge CB2 1TN, England

[36] Univ Med Ctr Hamburg Eppendorf, Dept Pediat Hematol & Oncol, D-20246 Hamburg, Germany

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

[38] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA

[39] Univ Toronto, Lab Med & Pathobiol, Toronto, ON M5G 1L7, Canada

来源：

CANCER CELL | 2015年 / 27卷 / 05期

关键词：

PEDIATRIC INTRACRANIAL EPENDYMOMAS; POSTERIOR-FOSSA EPENDYMOMAS; NF-KAPPA-B; MEDULLOBLASTOMA; MUTATIONS; SUBGROUPS; GENE; CHILDREN; SURVIVAL; SUPRATENTORIAL;

D O I：

10.1016/j.ccell.2015.04.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Ependymal tumors across age groups are currently classified and graded solely by histopathology. It is, however, commonly accepted that this classification scheme has limited clinical utility based on its lack of reproducibility in predicting patients' outcome. We aimed at establishing a uniform molecular classification using DNA methylation profiling. Nine molecular subgroups were identified in a large cohort of 500 tumors, 3 in each anatomical compartment of the CNS, spine, posterior fossa, supratentorial. Two supratentorial subgroups are characterized by prototypic fusion genes involving RELA and YAP1, respectively. Regarding clinical associations, the molecular classification proposed herein outperforms the current histopathological classification and thus might serve as a basis for the next World Health Organization classification of CNS tumors.

引用

页码：728 / 743

页数：16

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