TY  - JOUR
AU  - Sievers, Philipp
AU  - Henneken, Sophie
AU  - Blume, Christina
AU  - Sill, Martin
AU  - Schrimpf, Daniel
AU  - Stichel, Damian
AU  - Okonechnikov, Konstantin
AU  - Reuss, David E
AU  - Benzel, Julia
AU  - Maaß, Kendra K
AU  - Kool, Marcel
AU  - Sturm, Dominik
AU  - Zheng, Tuyu
AU  - Ghasemi, David R
AU  - Kohlhof-Meinecke, Patricia
AU  - Cruz, Ofelia
AU  - Suñol, Mariona
AU  - Lavarino, Cinzia
AU  - Ruf, Viktoria
AU  - Boldt, Henning B
AU  - Pagès, Mélanie
AU  - Pouget, Celso
AU  - Schweizer, Leonille
AU  - Kranendonk, Mariëtte E G
AU  - Akhtar, Noreen
AU  - Bunkowski, Stephanie
AU  - Stadelmann, Christine
AU  - Schüller, Ulrich
AU  - Mueller, Wolf C
AU  - Dohmen, Hildegard
AU  - Acker, Till
AU  - Harter, Patrick
AU  - Mawrin, Christian
AU  - Beschorner, Rudi
AU  - Brandner, Sebastian
AU  - Snuderl, Matija
AU  - Abdullaev, Zied
AU  - Aldape, Kenneth
AU  - Gilbert, Mark R
AU  - Armstrong, Terri S
AU  - Ellison, David W
AU  - Capper, David
AU  - Ichimura, Koichi
AU  - Reifenberger, Guido
AU  - Grundy, Richard G
AU  - Jabado, Nada
AU  - Krskova, Lenka
AU  - Zapotocky, Michal
AU  - Vicha, Ales
AU  - Varlet, Pascale
AU  - Wesseling, Pieter
AU  - Rutkowski, Stefan
AU  - Korshunov, Andrey
AU  - Wick, Wolfgang
AU  - Pfister, Stefan M
AU  - Jones, David T W
AU  - von Deimling, Andreas
AU  - Pajtler, Kristian W
AU  - Sahm, Felix
TI  - Recurrent fusions in PLAGL1 define a distinct subset of pediatric-type supratentorial neuroepithelial tumors.
JO  - Acta neuropathologica
VL  - 142
IS  - 5
SN  - 1432-0533
CY  - Heidelberg
PB  - Springer
M1  - DKFZ-2021-01763
SP  - 827-839
PY  - 2021
N1  - #EA:B300#LA:B300# / 2021 Nov;142(5):827-839
AB  - Ependymomas encompass a heterogeneous group of central nervous system (CNS) neoplasms that occur along the entire neuroaxis. In recent years, extensive (epi-)genomic profiling efforts have identified several molecular groups of ependymoma that are characterized by distinct molecular alterations and/or patterns. Based on unsupervised visualization of a large cohort of genome-wide DNA methylation data, we identified a highly distinct group of pediatric-type tumors (n = 40) forming a cluster separate from all established CNS tumor types, of which a high proportion were histopathologically diagnosed as ependymoma. RNA sequencing revealed recurrent fusions involving the pleomorphic adenoma gene-like 1 (PLAGL1) gene in 19 of 20 of the samples analyzed, with the most common fusion being EWSR1:PLAGL1 (n = 13). Five tumors showed a PLAGL1:FOXO1 fusion and one a PLAGL1:EP300 fusion. High transcript levels of PLAGL1 were noted in these tumors, with concurrent overexpression of the imprinted genes H19 and IGF2, which are regulated by PLAGL1. Histopathological review of cases with sufficient material (n = 16) demonstrated a broad morphological spectrum of tumors with predominant ependymoma-like features. Immunohistochemically, tumors were GFAP positive and OLIG2- and SOX10 negative. In 3/16 of the cases, a dot-like positivity for EMA was detected. All tumors in our series were located in the supratentorial compartment. Median age of the patients at the time of diagnosis was 6.2 years. Median progression-free survival was 35 months (for 11 patients with data available). In summary, our findings suggest the existence of a novel group of supratentorial neuroepithelial tumors that are characterized by recurrent PLAGL1 fusions and enriched for pediatric patients.
KW  - EP300 (Other)
KW  - EWSR1 (Other)
KW  - FOXO1 (Other)
KW  - Gene fusion (Other)
KW  - Neuroepithelial tumor (Other)
KW  - PLAGL1 (Other)
KW  - Supratentorial (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34355256
DO  - DOI:10.1007/s00401-021-02356-6
UR  - https://inrepo02.dkfz.de/record/170133
ER  -