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

Kristian W. Pajtler; Hendrik Witt; Martin Sill; David T.W. Jones; Volker Hovestadt; Fabian Kratochwil; Khalida Wani; Ruth Tatevossian; Chandanamali Punchihewa; Pascal Johann; Jüri Reimand; Hans Jörg Warnatz; Marina Ryzhova; Steve Mack; Vijay Ramaswamy; David Capper; Leonille Schweizer; Laura Sieber; Andrea Wittmann; Zhiqin Huang; Peter van Sluis; Richard Volckmann; Jan Koster; Rogier Versteeg; Daniel Fults; Helen Toledano; Smadar Avigad; Lindsey M. Hoffman; Andrew M. Donson; Nicholas Foreman; Ekkehard Hewer; Karel Zitterbart; Mark Gilbert; Terri S. Armstrong; Nalin Gupta; Jeffrey C. Allen; Matthias A. Karajannis; David Zagzag; Martin Hasselblatt; Andreas E. Kulozik; Olaf Witt; V. Peter Collins; Katja von Hoff; Stefan Rutkowski; Torsten Pietsch; Gary Bader; Marie Laure Yaspo; Andreas von Deimling; Peter Lichter; Michael D. Taylor; Richard Gilbertson; David W. Ellison; Kenneth Aldape; Andrey Korshunov; Marcel Kool; Stefan M. Pfister

doi:10.1016/j.ccell.2015.04.002

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

Kristian W. Pajtler, Hendrik Witt, Martin Sill, David T.W. Jones, Volker Hovestadt, Fabian Kratochwil, Khalida Wani, Ruth Tatevossian, Chandanamali Punchihewa, Pascal Johann, Jüri Reimand, Hans Jörg Warnatz, Marina Ryzhova, Steve Mack, Vijay Ramaswamy, David Capper, Leonille Schweizer, Laura Sieber, Andrea Wittmann, Zhiqin HuangPeter van Sluis, Richard Volckmann, Jan Koster, Rogier Versteeg, Daniel Fults, Helen Toledano, Smadar Avigad, Lindsey M. Hoffman, Andrew M. Donson, Nicholas Foreman, Ekkehard Hewer, Karel Zitterbart, Mark Gilbert, Terri S. Armstrong, Nalin Gupta, Jeffrey C. Allen, Matthias A. Karajannis, David Zagzag, Martin Hasselblatt, Andreas E. Kulozik, Olaf Witt, V. Peter Collins, Katja von Hoff, Stefan Rutkowski, Torsten Pietsch, Gary Bader, Marie Laure Yaspo, Andreas von Deimling, Peter Lichter, Michael D. Taylor, Richard Gilbertson, David W. Ellison, Kenneth Aldape, Andrey Korshunov, Marcel Kool^*, Stefan M. Pfister

^*Corresponding author for this work

Pathology

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927 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	728-743
Number of pages	16
Journal	Cancer Cell
Volume	27
Issue number	5
DOIs	https://doi.org/10.1016/j.ccell.2015.04.002
State	Published - 11 May 2015

Funding

Funders	Funder number
Collaborative Ependymoma Research Network
German Consortium for Translational Cancer Research
Making Headway Foundation
German Children’s Cancer Foundation
Heidelberger Zentrum für Personalisierte Onkologie Deutsches Krebsforschungszentrum In Der Helmholtz-Gemeinschaft
National Institutes of Health
National Center for the Advancement of Translational Science
Deutschen Konsortium für Translationale Krebsforschung
German Cancer Research Center-Heidelberg Center for Personalized Oncology
Stiftung Sibylle Assmus
Sander Stiftung
Clinical and Translational Science Institute, University of Pittsburgh
National Center for Tumor Diseases	CZ.1.05/2.1.00/03.0101
European Commission	340735
National Center for Advancing Translational Sciences	UL1TR000038, UL1TR001445
Cancer Center Support	P30CA016087, UL 1 TR000038
National Cancer Institute	P30CA016087, R01CA129541, R01CA121941

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10.1016/j.ccell.2015.04.002

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Pajtler, K. W., Witt, H., Sill, M., Jones, D. T. W., Hovestadt, V., Kratochwil, F., Wani, K., Tatevossian, R., Punchihewa, C., Johann, P., Reimand, J., Warnatz, H. J., Ryzhova, M., Mack, S., Ramaswamy, V., Capper, D., Schweizer, L., Sieber, L., Wittmann, A., ... Pfister, S. M. (2015). Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups. Cancer Cell, 27(5), 728-743. https://doi.org/10.1016/j.ccell.2015.04.002

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

abstract = "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.",

author = "Pajtler, {Kristian W.} and Hendrik Witt and Martin Sill and Jones, {David T.W.} and Volker Hovestadt and Fabian Kratochwil and Khalida Wani and Ruth Tatevossian and Chandanamali Punchihewa and Pascal Johann and J{\"u}ri Reimand and Warnatz, {Hans J{\"o}rg} and Marina Ryzhova and Steve Mack and Vijay Ramaswamy and David Capper and Leonille Schweizer and Laura Sieber and Andrea Wittmann and Zhiqin Huang and {van Sluis}, Peter and Richard Volckmann and Jan Koster and Rogier Versteeg and Daniel Fults and Helen Toledano and Smadar Avigad and Hoffman, {Lindsey M.} and Donson, {Andrew M.} and Nicholas Foreman and Ekkehard Hewer and Karel Zitterbart and Mark Gilbert and Armstrong, {Terri S.} and Nalin Gupta and Allen, {Jeffrey C.} and Karajannis, {Matthias A.} and David Zagzag and Martin Hasselblatt and Kulozik, {Andreas E.} and Olaf Witt and Collins, {V. Peter} and {von Hoff}, Katja and Stefan Rutkowski and Torsten Pietsch and Gary Bader and Yaspo, {Marie Laure} and {von Deimling}, Andreas and Peter Lichter and Taylor, {Michael D.} and Richard Gilbertson and Ellison, {David W.} and Kenneth Aldape and Andrey Korshunov and Marcel Kool and Pfister, {Stefan M.}",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = may,

day = "11",

doi = "10.1016/j.ccell.2015.04.002",

language = "אנגלית",

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Pajtler, KW, Witt, H, Sill, M, Jones, DTW, Hovestadt, V, Kratochwil, F, Wani, K, Tatevossian, R, Punchihewa, C, Johann, P, Reimand, J, Warnatz, HJ, Ryzhova, M, Mack, S, Ramaswamy, V, Capper, D, Schweizer, L, Sieber, L, Wittmann, A, Huang, Z, van Sluis, P, Volckmann, R, Koster, J, Versteeg, R, Fults, D, Toledano, H , Avigad, S, Hoffman, LM, Donson, AM, Foreman, N, Hewer, E, Zitterbart, K, Gilbert, M, Armstrong, TS, Gupta, N, Allen, JC, Karajannis, MA, Zagzag, D, Hasselblatt, M, Kulozik, AE, Witt, O, Collins, VP, von Hoff, K, Rutkowski, S, Pietsch, T, Bader, G, Yaspo, ML, von Deimling, A, Lichter, P, Taylor, MD, Gilbertson, R, Ellison, DW, Aldape, K, Korshunov, A, Kool, M & Pfister, SM 2015, 'Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups', Cancer Cell, vol. 27, no. 5, pp. 728-743. https://doi.org/10.1016/j.ccell.2015.04.002

TY - JOUR

T1 - Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups

AU - Pajtler, Kristian W.

AU - Witt, Hendrik

AU - Sill, Martin

AU - Jones, David T.W.

AU - Hovestadt, Volker

AU - Kratochwil, Fabian

AU - Wani, Khalida

AU - Tatevossian, Ruth

AU - Punchihewa, Chandanamali

AU - Johann, Pascal

AU - Reimand, Jüri

AU - Warnatz, Hans Jörg

AU - Ryzhova, Marina

AU - Mack, Steve

AU - Ramaswamy, Vijay

AU - Capper, David

AU - Schweizer, Leonille

AU - Sieber, Laura

AU - Wittmann, Andrea

AU - Huang, Zhiqin

AU - van Sluis, Peter

AU - Volckmann, Richard

AU - Koster, Jan

AU - Versteeg, Rogier

AU - Fults, Daniel

AU - Toledano, Helen

AU - Avigad, Smadar

AU - Hoffman, Lindsey M.

AU - Donson, Andrew M.

AU - Foreman, Nicholas

AU - Hewer, Ekkehard

AU - Zitterbart, Karel

AU - Gilbert, Mark

AU - Armstrong, Terri S.

AU - Gupta, Nalin

AU - Allen, Jeffrey C.

AU - Karajannis, Matthias A.

AU - Zagzag, David

AU - Hasselblatt, Martin

AU - Kulozik, Andreas E.

AU - Witt, Olaf

AU - Collins, V. Peter

AU - von Hoff, Katja

AU - Rutkowski, Stefan

AU - Pietsch, Torsten

AU - Bader, Gary

AU - Yaspo, Marie Laure

AU - von Deimling, Andreas

AU - Lichter, Peter

AU - Taylor, Michael D.

AU - Gilbertson, Richard

AU - Ellison, David W.

AU - Aldape, Kenneth

AU - Korshunov, Andrey

AU - Kool, Marcel

AU - Pfister, Stefan M.

PY - 2015/5/11

Y1 - 2015/5/11

N2 - 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.

AB - 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.

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U2 - 10.1016/j.ccell.2015.04.002

DO - 10.1016/j.ccell.2015.04.002

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C2 - 25965575

AN - SCOPUS:84929178049

SN - 1535-6108

VL - 27

SP - 728

EP - 743

JO - Cancer Cell

JF - Cancer Cell

IS - 5

ER -

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

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