TY  - JOUR
A1  - Alhalabi, Karam T.
A1  - Stichel, Damian
A1  - Sievers, Philipp
A1  - Peterziel, Heike
A1  - Sommerkamp, Alexander C.
A1  - Sturm, Dominik
A1  - Wittmann, Andrea
A1  - Sill, Martin
A1  - Jäger, Natalie
A1  - Beck, Pengbo
A1  - Pajtler, Kristian Wilfried
A1  - Snuderl, Matija
A1  - Jour, George
A1  - Delorenzo, Michael
A1  - Martin, Allison M.
A1  - Levy, Adam
A1  - Dalvi, Nagma
A1  - Hansford, Jordan R.
A1  - Gottardo, Nicholas G.
A1  - Uro-Coste, Emmanuelle
A1  - Maurage, Claude-Alain
A1  - Godfraind, Catherine
A1  - Vandenbos, Fanny
A1  - Pietsch, Torsten
A1  - Kramm, Christof M.
A1  - Filippidou, Maria
A1  - Kattamis, Antonis
A1  - Jones, Chris
A1  - Øra, Ingrid
A1  - Mikkelsen, Torben Stamm
A1  - Zapotocky, Michal
A1  - Sumerauer, David
A1  - Scheie, David
A1  - McCabe, Martin
A1  - Wesseling, Pieter
A1  - Tops, Bastiaan B. J.
A1  - Kranendonk, Mariëtte E. G.
A1  - Karajannis, Matthias A.
A1  - Bouvier, Nancy
A1  - Papaemmanuil, Elli
A1  - Dohmen, Hildegard
A1  - Acker, Till
A1  - Hoff, Katja von
A1  - Schmid, Simone
A1  - Miele, Evelina
A1  - Filipski, Katharina Johanna
A1  - Kitanovski, Lidija
A1  - Krskova, Lenka
A1  - Gojo, Johannes
A1  - Haberler, Christine
A1  - Alvaro, Frank
A1  - Ecker, Jonas
A1  - Selt, Florian
A1  - Milde, Till
A1  - Witt, Olaf
A1  - Oehme, Ina
A1  - Kool, Marcel
A1  - Deimling, Andreas von
A1  - Korshunov, Andrey
A1  - Pfister, Stefan
A1  - Sahm, Felix
A1  - Jones, David T. W.
T1  - PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum
T2  - Acta neuropathologica
N2  - 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.
KW  - Brain tumor
KW  - Pediatric
KW  - Neurooncology
KW  - Neuroepithelial
KW  - PATZ1
KW  - EWSR1
KW  - MN1
KW  - Gene fusion
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63567
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-635677
SN  - 1432-0533
N1  - This work was supported by the German Childhood Cancer Foundation (“Neuropath 2.0—Increasing diagnostic accuracy in pediatric neurooncology”; DKS 2015.01), the Everest Centre for Low-Grade Paediatric Brain Tumour Research (The Brain Tumour Charity, UK; GN-000382), the German Federal Ministry of Education and Research (BMBF), and Cancéropôle Lyon Auvergne Rhône-Alpes (CLARA). DNA methylation profiling at NYU was in part supported by grants from the Friedberg Charitable Foundation, the Sohn Conference Foundation and the Making Headway Foundation (to M. Snuderl.)
N1  - Open Access funding enabled and organized by Projekt DEAL.
VL  - 142
IS  - 5
SP  - 841
EP  - 857
PB  - Springer
CY  - Berlin ; Heidelberg
ER  -