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.

Department of Developmental Neurobiology St Jude Children's Research Hospital Memphis TN 38105 USA

Department of Molecular Oncology Schneider Children's Medical Center of Israel Tel Aviv University 49202 Tel Aviv Israel

Department of Neurological Surgery University of California San Francisco San Francisco CA 94143 USA

Department of Neuropathology NN Burdenko Neurosurgical Institute 125047 Moscow Russia

Department of Neuropathology University of Bonn 53127 Bonn Germany

Department of Neuropathology University of Heidelberg 69120 Heidelberg Germany; Clinical Cooperation Unit Neuropathology German Cancer Research Center 69120 Heidelberg Germany

Department of Oncogenomics Academic Medical Center 1105AZ Amsterdam the Netherlands

Department of Pathology NYU Langone Medical Center New York NY 10016 USA

Department of Pathology St Jude Children's Research Hospital Memphis TN 38105 USA

Department of Pathology University of Bern 3010 Bern Switzerland

Department of Pathology University of Cambridge Cambridge CB2 1TN UK

Department of Pediatric Hematology and Oncology University Medical Center Hamburg Eppendorf 20246 Hamburg Germany

Department of Pediatric Oncology Faculty of Medicine University Hospital Brno and Masaryk University 61300 Brno Czech Republic; Regional Centre for Applied Molecular Oncology Masaryk Memorial Cancer Institute 65653 Brno Czech Republic

Department of Pediatric Oncology Hematology and Immunology University Hospital 69120 Heidelberg Germany

Department of Pediatric Oncology Hematology and Immunology University Hospital 69120 Heidelberg Germany; Clinical Cooperation Unit Pediatric Oncology German Cancer Research Center 69120 Heidelberg Germany

Department of Pediatrics University of Colorado Denver Aurora CO 80045 USA

Department of Translational Molecular Pathology University of Texas MD Anderson Cancer Center Houston TX 77030 USA

Department of Vertebrate Genomics Max Planck Institute for Molecular Genetics 14195 Berlin Germany

Departments of Pediatrics and Neurology NYU Langone Medical Center New York NY 10016 USA

Division of Biostatistics German Cancer Research Center 69120 Heidelberg Germany

Division of Cancer Medicine Department of Neuro Oncology The University of Texas MD Anderson Cancer Center Houston TX 77030 USA

Division of Cancer Medicine Department of Neuro Oncology The University of Texas MD Anderson Cancer Center Houston TX 77030 USA; Department of Family Health University of Texas Health Science Center SON Houston TX 77030 USA

Division of Molecular Genetics German Cancer Research Center 69120 Heidelberg Germany

Division of Neurosurgery Arthur and Sonia Labatt Brain Tumour Research Centre The Hospital for Sick Children Toronto ON M5G 1X8 Canada

Division of Neurosurgery Arthur and Sonia Labatt Brain Tumour Research Centre The Hospital for Sick Children Toronto ON M5G 1X8 Canada; Division of Hematology Oncology Hospital for Sick Children Toronto ON M5G 1X8 Canada

Division of Pediatric Hematology and Oncology Departments of Pediatrics and Otolaryngology NYU Langone Medical Center New York NY 10016 USA

Division of Pediatric Neurooncology German Cancer Research Center 69120 Heidelberg Germany

Division of Pediatric Neurooncology German Cancer Research Center 69120 Heidelberg Germany; Department of Pediatric Oncology and Hematology University Children's Hospital Essen 45147 Essen Germany

German Cancer Consortium 69120 Heidelberg Germany

Institute for Neuropathology University Hospital Münster 48149 Münster Germany

Laboratory Medicine and Pathobiology University of Toronto Toronto ON M5G 1L7 Canada

Pediatric Hematology Oncology Schneider Children's Medical Center of Israel 49202 Petah Tikva Israel

The Donnelly Center University of Toronto Toronto ON M5S 3E1 Canada

University of Utah Salt Lake City UT 84132 USA

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Cancer Cell. 2015 May 11;27(5):613-5. doi: 10.1016/j.ccell.2015.04.015. PubMed

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GEO
GSE64415, GSE65362