- Title
- PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum
- Creator
- Alhalabi, Karam T.; Stichel, Damian; 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; Sievers, Philipp; Alvaro, Frank; Godfraind, C; Vandenbos, F; Pietsch, T; Kramm, C; Filippidou, M; Kattamis, A; Jones, C; Ora, I; Mikkelsen, TS; Peterziel, Heike; Zapotocky, M; Sumerauer, D; Scheie, D; McCabe, M; Wesseling, P; Tops, BBJ; Kranendonk, MEG; Karajannis, MA; Bouvier, N; Papaemmanuil, E; Sommerkamp, Alexander C.; Dohmen, H; Acker, T; von Hoff, K; Schmid, S; Miele, E; Filipski, K; Kitanovski, L; Krskova, L; Gojo, J; Haberler, C; Sturm, Dominik; Alvaro, F; Ecker, J; Selt, F; Milde, T; Witt, O; Oehme, I; Kool, M; von Deimling, A; Korshunov, A; Pfister, SM; Wittmann, Andrea; Sahm, F; Jones, DTW; Sill, Martin; Jäger, Natalie; Beck, Pengbo
- Relation
- Acta Neuropathologica Vol. 142, Issue 5, p. 841-857
- Publisher Link
- http://dx.doi.org/10.1007/s00401-021-02354-8
- Publisher
- Springer
- Resource Type
- journal article
- Date
- 2021
- Description
- 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.
- Subject
- brain tumor; pediatric; neurooncology; neuroepithelial; PATZ1; EWSR1; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1470488
- Identifier
- uon:48482
- Identifier
- ISSN:0001-6322
- Language
- eng
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