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Cancer Cell. 2015 May 11;27(5):728-43. doi: 10.1016/j.ccell.2015.04.002.

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

Author information

1
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Department of Pediatric Oncology and Hematology, University Children's Hospital Essen, 45147 Essen, Germany.
2
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Department of Pediatric Oncology, Hematology and Immunology, University Hospital, 69120 Heidelberg, Germany; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.
3
Division of Biostatistics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
4
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
5
Division of Molecular Genetics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
6
Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
7
Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
8
The Donnelly Center, University of Toronto, Toronto, ON M5S 3E1, Canada.
9
Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
10
Department of Neuropathology, NN Burdenko Neurosurgical Institute, 125047 Moscow, Russia.
11
Division of Neurosurgery, Arthur & Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
12
Division of Neurosurgery, Arthur & 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.
13
Department of Neuropathology, University of Heidelberg, 69120 Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
14
Department of Oncogenomics, Academic Medical Center, 1105AZ Amsterdam, the Netherlands.
15
University of Utah, Salt Lake City, UT 84132, USA.
16
Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, 49202 Petah Tikva, Israel.
17
Department of Molecular Oncology, Schneider Children's Medical Center of Israel, Tel Aviv University, 49202 Tel Aviv, Israel.
18
Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, USA.
19
Department of Pathology, University of Bern, 3010 Bern, Switzerland.
20
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.
21
Division of Cancer Medicine, Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
22
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.
23
Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
24
Departments of Pediatrics and Neurology, NYU Langone Medical Center, New York, NY 10016, USA.
25
Division of Pediatric Hematology and Oncology, Departments of Pediatrics and Otolaryngology, NYU Langone Medical Center, New York, NY 10016, USA.
26
Department of Pathology, NYU Langone Medical Center, New York, NY 10016, USA.
27
Institute for Neuropathology, University Hospital Münster, 48149 Münster, Germany.
28
Department of Pediatric Oncology, Hematology and Immunology, University Hospital, 69120 Heidelberg, Germany.
29
Department of Pediatric Oncology, Hematology and Immunology, University Hospital, 69120 Heidelberg, Germany; Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
30
Department of Pathology, University of Cambridge, Cambridge CB2 1TN, UK.
31
Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
32
Department of Neuropathology, University of Bonn, 53127 Bonn, Germany.
33
German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; Division of Molecular Genetics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
34
Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
35
Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1L7, Canada.
36
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. Electronic address: m.kool@dkfz.de.
37
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Department of Pediatric Oncology, Hematology and Immunology, University Hospital, 69120 Heidelberg, Germany; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany. Electronic address: s.pfister@dkfz.de.

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.

PMID:
25965575
PMCID:
PMC4712639
DOI:
10.1016/j.ccell.2015.04.002
[Indexed for MEDLINE]
Free PMC Article
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