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- Article (17)
- Conference Proceeding (1)
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- English (18)
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- yes (18)
Is part of the Bibliography
- no (18)
Keywords
- Brain tumor (1)
- EWSR1 (1)
- Gene fusion (1)
- MN1 (1)
- Neuroepithelial (1)
- Neurooncology (1)
- PATZ1 (1)
- Pediatric (1)
Institute
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Alhalabi, Karam T. ; Stichel, Damian ; Sievers, Philipp ; Peterziel, Heike ; Sommerkamp, Alexander C. ; Sturm, Dominik ; Wittmann, Andrea ; Sill, Martin ; Jäger, Natalie ; Beck, Pengbo ; Pajtler, Kristian Wilfried ; Snuderl, Matija ; Jour, George ; Delorenzo, Michael ; Martin, Allison M. ; Levy, Adam ; Dalvi, Nagma ; Hansford, Jordan R. ; Gottardo, Nicholas G. ; Uro-Coste, Emmanuelle ; Maurage, Claude-Alain ; Godfraind, Catherine ; Vandenbos, Fanny ; Pietsch, Torsten ; Kramm, Christof M. ; Filippidou, Maria ; Kattamis, Antonis ; Jones, Chris ; Øra, Ingrid ; Mikkelsen, Torben Stamm ; Zapotocky, Michal ; Sumerauer, David ; Scheie, David ; McCabe, Martin ; Wesseling, Pieter ; Tops, Bastiaan B. J. ; Kranendonk, Mariëtte E. G. ; Karajannis, Matthias A. ; Bouvier, Nancy ; Papaemmanuil, Elli ; Dohmen, Hildegard ; Acker, Till ; Hoff, Katja von ; Schmid, Simone ; Miele, Evelina ; Filipski, Katharina Johanna ; Kitanovski, Lidija ; Krskova, Lenka ; Gojo, Johannes ; Haberler, Christine ; Alvaro, Frank ; Ecker, Jonas ; Selt, Florian ; Milde, Till ; Witt, Olaf ; Oehme, Ina ; Kool, Marcel ; Deimling, Andreas von ; Korshunov, Andrey ; Pfister, Stefan ; Sahm, Felix ; Jones, David T. W.
Large-scale molecular profiling studies in recent years have shown that central nervous system (CNS) tumors display a much greater heterogeneity in terms of molecularly distinct entities, cellular origins and genetic drivers than anticipated from histological assessment. DNA methylation profiling has emerged as a useful tool for robust tumor classification, providing new insights into these heterogeneous molecular classes. This is particularly true for rare CNS tumors with a broad morphological spectrum, which are not possible to assign as separate entities based on histological similarity alone. Here, we describe a molecularly distinct subset of predominantly pediatric CNS neoplasms (n = 60) that harbor PATZ1 fusions. The original histological diagnoses of these tumors covered a wide spectrum of tumor types and malignancy grades. While the single most common diagnosis was glioblastoma (GBM), clinical data of the PATZ1-fused tumors showed a better prognosis than typical GBM, despite frequent relapses. RNA sequencing revealed recurrent MN1:PATZ1 or EWSR1:PATZ1 fusions related to (often extensive) copy number variations on chromosome 22, where PATZ1 and the two fusion partners are located. These fusions have individually been reported in a number of glial/glioneuronal tumors, as well as extracranial sarcomas. We show here that they are more common than previously acknowledged, and together define a biologically distinct CNS tumor type with high expression of neural development markers such as PAX2, GATA2 and IGF2. Drug screening performed on the MN1:PATZ1 fusion-bearing KS-1 brain tumor cell line revealed preliminary candidates for further study. In summary, PATZ1 fusions define a molecular class of histologically polyphenotypic neuroepithelial tumors, which show an intermediate prognosis under current treatment regimens.