Journalartikel
Autorenliste: Alhalabi, Karam T.; Stichel, Damian; Sievers, Philipp; Peterziel, Heike; Sommerkamp, Alexander C.; Sturm, Dominik; Wittmann, Andrea; Sill, Martin; Jaeger, Natalie; Beck, Pengbo; Pajtler, Kristian W.; 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; Filippidou, Maria; Kattamis, Antonis; Jones, Chris; Ora, Ingrid; Mikkelsen, Torben Stamm; Zapotocky, Michal; Sumerauer, David; Scheie, David; McCabe, Martin; Wesseling, Pieter; Tops, Bastiaan B. J.; Kranendonk, Mariette E. G.; Karajannis, Matthias A.; Bouvier, Nancy; Papaemmanuil, Elli; Dohmen, Hildegard; Acker, Till; von Hoff, Katja; Schmid, Simone; Miele, Evelina; Filipski, Katharina; Kitanovski, Lidija; Krskova, Lenka; Gojo, Johannes; Haberler, Christine; Alvaro, Frank; Ecker, Jonas; Selt, Florian; Milde, Till; Witt, Olaf; Oehme, Ina; Kool, Marcel; von Deimling, Andreas; Korshunov, Andrey; Pfister, Stefan M.; Sahm, Felix; Jones, David T. W.
Jahr der Veröffentlichung: 2021
Seiten: 841-857
Zeitschrift: Acta Neuropathologica
Bandnummer: 142
Heftnummer: 5
ISSN: 0001-6322
eISSN: 1432-0533
DOI Link: https://doi.org/10.1007/s00401-021-02354-8
Verlag: Springer
Abstract:
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.
Zitierstile
Harvard-Zitierstil: Alhalabi, K., Stichel, D., Sievers, P., Peterziel, H., Sommerkamp, A., Sturm, D., et al. (2021) PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum, Acta Neuropathologica, 142(5), pp. 841-857. https://doi.org/10.1007/s00401-021-02354-8
APA-Zitierstil: Alhalabi, K., Stichel, D., Sievers, P., Peterziel, H., Sommerkamp, A., Sturm, D., Wittmann, A., Sill, M., Jaeger, N., Beck, P., Pajtler, K., Snuderl, M., Jour, G., Delorenzo, M., Martin, A., Levy, A., Dalvi, N., Hansford, J., Gottardo, N., ...Jones, D. (2021). PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum. Acta Neuropathologica. 142(5), 841-857. https://doi.org/10.1007/s00401-021-02354-8
Schlagwörter
EWSR1; GATA2; GENE FUSION; GENETIC ALTERATIONS; METHYLATION-BASED CLASSIFICATION; MIDBRAIN; MN1; Neuroepithelial; Neurooncology; PATZ1; Pediatric; PEDIATRIC HIGH-GRADE
