MYCN amplification drives an aggressive form of spinal ependymoma

• DOI: 10.1007/s00401-019-02056-2
• Publication Date: 2019-08-14T23:03:00Z
• Authors: David R. Ghasemi; Martin Sill; Konstantin Okonec...; Andrey Korshunov; Stephen Yip; Peter W. Schutz; David Scheie; Anders Kruse; Patrick N. Harter; Marina Kastelan; Marlies Wagner; Christian Hartmann; Julia Benzel; Kendra K. Maass; Mustafa Khasraw; Ronald Sträter; Christian Thomas; Werner Paulus; Christian P. Kratz; Hendrik Witt; Daisuke Kawauchi; Christel Herold-M...; Felix Sahm; Sebastian Brandner; Marcel Kool; David T. W. Jones; Andreas von Deimling; Stefan M. Pfister; David E. Reuss; Kristian W. Pajtler
• Keywords: Ependymoma

Spinal ependymal tumors form a histologically and molecularly heterogeneous group of with generally good prognosis. However, their treatment can be challenging if infiltration the spinal cord or dissemination throughout central nervous system (CNS) occurs and, in these cases, clinical outcome remains poor. Here, we describe new relatively rare subgroup identified using DNA methylation profiling that is distinct from other molecular subgroups ependymoma. Copy number variation plots derived arrays showed MYCN amplification as characteristic genetic alteration all cases our cohort (n = 13), which was subsequently validated fluorescence situ hybridization. The histological diagnosis anaplastic ependymoma (WHO Grade III) ten classic II) three cases. Histological re-evaluation five primary seven relapses features ependymoma, namely pseudorosettes, GFAP- EMA positivity. Electron microscopy revealed cilia, complex intercellular junctions intermediate filaments representative sample. Taking findings into account, suggest to designate this amplification, SP-EPN-MYCN. SP-EPN-MYCN growth patterns intradural, extramedullary localization mostly within thoracic cervical spine, diffuse leptomeningeal spread whole CNS infiltrative invasion cord. Dissemination observed 100% Despite high-intensity treatment, significantly worse median progression free survival (PFS) (17 months) overall (OS) (87 than previously described subgroups. OS PFS were similar supratentorial RELA-fusion (ST-EPN-RELA) posterior fossa A (PF-EPN-A), further highlighting aggressiveness subgroup. We, therefore, propose establish advocate for testing newly diagnosed amplification.