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:https://doi.org/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

Research output: Contribution to journal › Article › Academic › peer-review

844 Citations (Scopus)

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
Journal	Cancer cell
Volume	27
Issue number	5
DOIs	https://doi.org/10.1016/j.ccell.2015.04.002
Publication status	Published - 2015

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https://doi.org/10.1016/j.ccell.2015.04.002

Cite this

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

@article{45bf543efe744467bdfb0e0b2db7708c,

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 Hans-J{\"o}rg Warnatz 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 Marie-Laure Yaspo 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.}",

year = "2015",

doi = "https://doi.org/10.1016/j.ccell.2015.04.002",

language = "English",

volume = "27",

pages = "728--743",

journal = "Cancer cell",

issn = "1535-6108",

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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, H-J, 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, M-L, 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

Y1 - 2015

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

U2 - https://doi.org/10.1016/j.ccell.2015.04.002

DO - https://doi.org/10.1016/j.ccell.2015.04.002

M3 - Article

C2 - 25965575

SN - 1535-6108

VL - 27

SP - 728

EP - 743

JO - Cancer cell

JF - Cancer cell

IS - 5

ER -