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Neuro Oncol. 2018 Nov 12;20(12):1616-1624. doi: 10.1093/neuonc/noy118.

DNA methylation-based classification of ependymomas in adulthood: implications for diagnosis and treatment.

Author information

1
Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
2
Division of Pediatric Neuro-oncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
3
Department of Pediatric Oncology, Hematology, and Immunology, University Hospital Heidelberg, Heidelberg, Germany.
4
Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.
5
Institute for Medical Informatics, Statistics, and Epidemiology, University of Leipzig, Leipzig, Germany.
6
Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany.
7
German Cancer Consortium(DKTK), partner site Essen/Düsseldorf, German Cancer Research Center(DKFZ), Heidelberg, Germany.
8
Department of Neurosurgery, Carl Gustav Carus University Hospital, Technical University of Dresden, Dresden, Germany.
9
Spine Center DWG Level I, Carl Gustav Carus University Hospital, Technical University of Dresden, Dresden, Germany.
10
Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany.
11
Clinical Cooperation Unit Neuropathology, German Cancer Consortium(DKTK), German Cancer Research Center(DKFZ), Heidelberg, Germany.
12
Department of Neuropathology, Charité Universitätsmedizin Berlin and German Cancer Consortium(DKTK), partner site Berlin, Germany.
13
Department of Neurology, Division of Clinical Neuro-oncology, University of Bonn Medical Center, Bonn, Germany.
14
Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
15
Department of Neuropathology, University of Bonn, Bonn, Germany.
16
Department of Neurosurgery, University of Munich LMU, Munich, Germany.

Abstract

Background:

Ependymal tumors are glial tumors that commonly manifest in children and young adults. Their classification has remained entirely morphological until recently, and surgery and radiotherapy are the main treatment options, especially in adults. Here we sought to correlate DNA methylation profiles with clinical and pathological characteristics in the prospective cohort of the German Glioma Network.

Methods:

Tumors from 122 adult patients with myxopapillary ependymoma, ependymoma, anaplastic ependymoma, subependymoma, or RELA fusion-positive ependymoma classified according to the World Health Organization (WHO) 2016 were subjected to DNA methylation profiling using the Illumina HumanMethylation450 BeadChip platform. Molecular data were correlated with histologic features and clinical characteristics.

Results:

At a median follow-up of 86.7 months, only 22 patients experienced progression (18.0%) and 13 patients (10.7%) died. Each tumor could be assigned to one of the previously defined molecular ependymoma subgroups. All histologic subependymomas corresponded to subependymoma (SE) DNA methylation subgroups, but the reverse was not true: 19 histologic ependymomas (WHO grade II) were allocated to molecular SE groups. Similarly, all histological myxopapillary ependymomas were assigned to the molecularly defined spinal myxopapillary ependymoma (SP-MPE) class, but this molecular subgroup additionally included 15 WHO grade II ependymomas by histology. Overall, WHO grade II ependymomas distributed into 7 molecular subgroups.

Conclusion:

Most adult patients with ependymoma show a favorable prognosis. Molecular classification may provide diagnostic and prognostic information beyond histology and facilitate patient stratification in future clinical trials. The prognostic significance of a subependymoma or myxopapillary ependymoma DNA methylation phenotype without corresponding histology requires further study.

Key Points:

1. Ependymoma diagnosed in adult patients most often shows a good prognosis. 2. Molecular classification can support diagnostic and prognostic information beyond histology.

PMID:
30053291
PMCID:
PMC6231197
[Available on 2019-11-12]
DOI:
10.1093/neuonc/noy118

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