TY  - JOUR
AU  - Ghasemi, David R
AU  - Sill, Martin
AU  - Okonechnikov, Konstantin
AU  - Korshunov, Andrey
AU  - Yip, Stephen
AU  - Schutz, Peter W
AU  - Scheie, David
AU  - Kruse, Anders
AU  - Harter, Patrick N
AU  - Kastelan, Marina
AU  - Wagner, Marlies
AU  - Hartmann, Christian
AU  - Benzel, Julia
AU  - Maass, Kendra K
AU  - Khasraw, Mustafa
AU  - Sträter, Ronald
AU  - Thomas, Christian
AU  - Paulus, Werner
AU  - Kratz, Christian P
AU  - Witt, Hendrik
AU  - Kawauchi, Daisuke
AU  - Herold-Mende, Christel
AU  - Sahm, Felix
AU  - Brandner, Sebastian
AU  - Kool, Marcel
AU  - Jones, David T W
AU  - von Deimling, Andreas
AU  - Pfister, Stefan M
AU  - Reuss, David E
AU  - Pajtler, Kristian
TI  - MYCN amplification drives an aggressive form of spinal ependymoma.
JO  - Acta neuropathologica
VL  - 138
IS  - 6
SN  - 1432-0533
CY  - Heidelberg
PB  - Springer
M1  - DKFZ-2019-02024
SP  - 1075-1089
PY  - 2019
N1  - 138(6):1075-1089
AB  - Spinal ependymal tumors form a histologically and molecularly heterogeneous group of tumors with generally good prognosis. However, their treatment can be challenging if infiltration of the spinal cord or dissemination throughout the central nervous system (CNS) occurs and, in these cases, clinical outcome remains poor. Here, we describe a new and relatively rare subgroup of spinal ependymal tumors identified using DNA methylation profiling that is distinct from other molecular subgroups of ependymoma. Copy number variation plots derived from DNA methylation arrays showed MYCN amplification as a characteristic genetic alteration in all cases of our cohort (n = 13), which was subsequently validated using fluorescence in situ hybridization. The histological diagnosis was anaplastic ependymoma (WHO Grade III) in ten cases and classic ependymoma (WHO Grade II) in three cases. Histological re-evaluation in five primary tumors and seven relapses showed characteristic histological features of ependymoma, namely pseudorosettes, GFAP- and EMA positivity. Electron microscopy revealed cilia, complex intercellular junctions and intermediate filaments in a representative sample. Taking these findings into account, we suggest to designate this molecular subgroup spinal ependymoma with MYCN amplification, SP-EPN-MYCN. SP-EPN-MYCN tumors showed distinct growth patterns with intradural, extramedullary localization mostly within the thoracic and cervical spine, diffuse leptomeningeal spread throughout the whole CNS and infiltrative invasion of the spinal cord. Dissemination was observed in 100
LB  - PUB:(DE-HGF)16
C6  - pmid:31414211
DO  - DOI:10.1007/s00401-019-02056-2
UR  - https://inrepo02.dkfz.de/record/144581
ER  -