PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum Journal Article

   

Authors:	Alhalabi, K. T.; Stichel, D.; Sievers, P.; Peterziel, H.; Sommerkamp, A. C.; Sturm, D.; Wittmann, A.; Sill, M.; Jäger, N.; Beck, P.; Pajtler, K. W.; Snuderl, M.; Jour, G.; Delorenzo, M.; Martin, A. M.; Levy, A.; Dalvi, N.; Hansford, J. R.; Gottardo, N. G.; Uro-Coste, E.; Maurage, C. A.; Godfraind, C.; Vandenbos, F.; Pietsch, T.; Kramm, C.; Filippidou, M.; Kattamis, A.; Jones, C.; Øra, I.; Stamm Mikkelsen, T. S.; Zapotocky, M.; Sumerauer, D.; Scheie, D.; McCabe, M.; Wesseling, P.; Tops, B. B. J.; Kranendonk, M. E. G.; Karajannis, M. A.; Bouvier, N.; Papaemmanuil, E.; Dohmen, H.; Acker, T.; von Hoff, K.; Schmid, S.; Miele, E.; Filipski, K.; Kitanovski, L.; Krskova, L.; Gojo, J.; Haberler, C.; Alvaro, F.; Ecker, J.; Selt, F.; Milde, T.; Witt, O.; Oehme, I.; Kool, M.; von Deimling, A.; Korshunov, A.; Pfister, S. M.; Sahm, F.; Jones, D. T. W.
Article Title:	PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum
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. © 2021, The Author(s).
Keywords:	brain tumor; pediatric; gene fusion; neurooncology; ewsr1; neuroepithelial; patz1; mn1
Journal Title:	Acta Neuropathologica
Volume:	142
Issue:	5
ISSN:	0001-6322
Publisher:	Springer
Date Published:	2021-11-01
Start Page:	841
End Page:	857
Language:	English
PMCID:	PMC8500868
DOI:	10.1007/s00401-021-02354-8
PROVIDER:	scopus
PUBMED:	34417833
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85113151225&doi=10.1007%2fs00401-021-02354-8&partnerID=40&md5=e1df5435825a2675a910a7c98600820f
Notes:	Article -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/188871