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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)728-743
Number of pages16
JournalCancer Cell
Volume27
Issue number5
DOIs
StatePublished - 11 May 2015

Funding

FundersFunder number
Cancer Center SupportUL 1 TR000038
Collaborative Ependymoma Research Network
German Cancer Research Center-Heidelberg Center for Personalized Oncology
German Children’s Cancer Foundation
German Consortium for Translational Cancer Research
National Center for Tumor DiseasesCZ.1.05/2.1.00/03.0101
National Center for the Advancement of Translational Science
Sander Stiftung
Stiftung Sibylle Assmus
National Institutes of HealthP30CA016087
National Institutes of Health
National Cancer InstituteR01CA121941
National Cancer Institute
Clinical and Translational Science Institute, University of Pittsburgh
Heidelberger Zentrum für Personalisierte Onkologie Deutsches Krebsforschungszentrum In Der Helmholtz-Gemeinschaft
Making Headway Foundation
Deutschen Konsortium für Translationale Krebsforschung

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