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

Hendrik Witt, Dorothee Gramatzki, Bettina Hentschel, Kristian W. Pajtler, Jörg Felsberg, Gabriele Schackert, Markus Löffler, David Capper, Felix Sahm, Martin Sill, Andreas Von Deimling, Marcel Kool, Ulrich Herrlinger, Manfred Westphal, Torsten Pietsch, Guido Reifenberger, Stefan M. Pfister, Jörg C. Tonn, Michael Weller

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

62 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)1616-1624
Aantal pagina's9
TijdschriftNeuro-Oncology
Volume20
Nummer van het tijdschrift12
DOI's
StatusGepubliceerd - 12 nov. 2018
Extern gepubliceerdJa

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