Delineation of Two Clinically and Molecularly Distinct Subgroups of Posterior Fossa Ependymoma

Authors

• Hendrik Witt, German Cancer Research Center
• Stephen C. Mack, Hospital for Sick Children
• Marina Ryzhova, NN Burdenko Neurosurgical Institute
• Sebastian Bender, German Cancer Research Center
• Martin Sill, German Cancer Research Center
• Ruth Isserlin, University of Toronto
• Axel Benner, German Cancer Research Center
• Thomas Hielscher, German Cancer Research Center
• Till Milde, University Hospital Heidelberg
• Marc Remke, German Cancer Research Center
• David T. W. Jones, German Cancer Research Center
• Paul A. Northcott, Hospital for Sick Children
• Livia Garzia, Hospital for Sick Children
• Kelsey C. Bertrand, Hospital for Sick Children
• Andrea Wittmann, German Cancer Research Center
• Yuan Yao, Hospital for Sick Children, Toronto
• Stephen S. Roberts, Uniformed Services University of the Health Sciences
• Luca Massimi, Catholic University School of Medicine
• Tim Van Meter, Virginia Commonwealth University
• William A. Weiss, University of California - San Francisco
• Nalin Gupta, University of California - San Francisco
• Wiesia Grajkowska, University of Warsaw
• Boleslaw Lach, McMaster University
• Yoon-Jae Cho, Children’s Hospital Boston
• Andreas von Deimling, University of Heidelberg
• Andreas E. Kulozik, University Hospital Heidelberg
• Olaf Witt, University Hospital Heidelberg
• Gary D. Bader, University of Toronto
• Cynthia E. Hawkins, Hospital for Sick Children
• Uri Tabori, Hospital for Sick Children
• Abhijit Guha, Hospital for Sick Children
• James T. Rutka, Hospital for Sick Children
• Peter Lichter, German Cancer Research Center
• Andrey Korshunov, University of Heidelberg
• Michael D. Taylor, Hospital for Sick ChildrenFollow
• Stefan M. Pfister, German Cancer Research CenterFollow

Date of this Version

2011

Comments

Published in Cancer Cell (2011) 20, 143–157; DOI 10.1016/j.ccr.2011.07.007

Abstract

Despite the histological similarity of ependymomas from throughout the neuroaxis, the disease likely comprises multiple independent entities, each with a distinct molecular pathogenesis. Transcriptional profiling of two large independent cohorts of ependymoma reveals the existence of two demographically, transcriptionally, genetically, and clinically distinct groups of posterior fossa (PF) ependymomas. Group A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, metastasis at recurrence, and death compared with Group B patients. Identification and optimization of immunohistochemical (IHC) markers for PF ependymoma subgroups allowed validation of our findings on a third independent cohort, using a human ependymoma tissue microarray, and provides a tool for prospective prognostication and stratification of PF ependymoma patients.