TY  - JOUR
AU  - Tauziède-Espariat, Arnault
AU  - Dangouloff-Ros, Volodia
AU  - Sievers, Philipp
AU  - Duchesne, Mathilde
AU  - Siegfried, Aurore
AU  - Nicaise, Yvan
AU  - Boddaert, Nathalie
AU  - Hasty, Lauren
AU  - Métais, Alice
AU  - Ngo, Carine
AU  - le Loarer, François
AU  - Bouvier, Corinne
AU  - Fontaine, Alix
AU  - Rousseau, Audrey
AU  - Marguet, Florent
AU  - Beccaria, Kévin
AU  - Blauwblomme, Thomas
AU  - Uro-Coste, Emmanuelle
AU  - Varlet, Pascale
TI  - Glioneuronal tumors PATZ1-fused: clinico-molecular and DNA methylation signatures for a variety of morphological and radiological profiles.
JO  - Acta Neuropathologica Communications
VL  - 13
IS  - 1
SN  - 2051-5960
CY  - London
PB  - Biomed Central
M1  - DKFZ-2025-01083
SP  - 114
PY  - 2025
AB  - The neuroepithelial tumor, PATZ1-fused (NET-PATZ1), has been recently isolated as a distinct methylation class by DNA-methylation profiling and is characterized by recurrent PATZ1 fusions, in association with the EWSR1 or MN1 genes and a chromosome 22 chromothripsis. The clinical phenotype is mainly pediatric and features circumscribed supratentorial tumors. However, the histopathology is vastly heterogeneous (glial, glioneuronal, sarcomatous, multiphenotypic) and a cell of origin has not yet been identified, explaining the previsionary imprecise terminology of 'NET'. Moreover, extra-central nervous system (CNS) sarcomas also harboring the EWSR1::PATZ1 fusion have been reported and added to the current World Health Organization (WHO) Classification of Soft Tissue and Bone Tumors, in the chapter on undifferentiated small round cell sarcomas. However, their relationship to their CNS counterparts has not yet been studied. Herein, we analyzed a cohort of twelve CNS tumors with PATZ1 fusions in terms of clinical presentation, radiology, histopathology, immunohistochemistry, ultrastructure and DNA-methylation profiling and compared them to five extra-CNS sarcomas-PATZ1. Based on the reported GATA2 overexpression in NET-PATZ1, we also studied the potential interest of GATA2 immunoexpression as a diagnostic tool. We confirmed their distinct molecular characteristics and clinical phenotype but evidenced a morphological intratumoral heterogeneity with three recurrent morphological patterns (oligodendroglial-like, pleomorphic xanthoastrocytoma-like and spindle cells). Despite the unusual spindle and proliferative component in a CD34 + glioneuronal tumor (using electronic microscopy), these tumors present a favorable prognosis. Their histopathological features were all clearly distinct from their soft tissue counterparts. GATA2 immunostaining is highly specific for CNS tumors PATZ1-fused, but its sensitivity is perfectible and further studies are needed to confirm its use as a diagnostic tool. To conclude, our work highlights that CNS tumors, PATZ1-fused seem to represent a novel pediatric glioneuronal tumor type exhibiting a polymorphous morphology and provides new support for its addition as a provisional emerging pediatric circumscribed glioneuronal tumor type, low grade.
KW  - Humans
KW  - DNA Methylation: genetics
KW  - Male
KW  - Female
KW  - Child
KW  - Adolescent
KW  - Child, Preschool
KW  - Adult
KW  - Young Adult
KW  - Repressor Proteins: genetics
KW  - Repressor Proteins: metabolism
KW  - Neoplasms, Neuroepithelial: genetics
KW  - Neoplasms, Neuroepithelial: pathology
KW  - Neoplasms, Neuroepithelial: diagnostic imaging
KW  - Co-Repressor Proteins
KW  - Middle Aged
KW  - Central Nervous System Neoplasms: genetics
KW  - Central Nervous System Neoplasms: pathology
KW  - Central Nervous System Neoplasms: diagnostic imaging
KW  - Oncogene Proteins, Fusion: genetics
KW  - RNA-Binding Protein EWS: genetics
KW  - Infant
KW  - Kruppel-Like Transcription Factors
KW  - DNA-methylation (Other)
KW  - EWSR1::PATZ1 (Other)
KW  - Glioneuronal tumor (Other)
KW  - MN1::PATZ1 (Other)
KW  - PATZ1 protein, human (NLM Chemicals)
KW  - Repressor Proteins (NLM Chemicals)
KW  - Co-Repressor Proteins (NLM Chemicals)
KW  - Oncogene Proteins, Fusion (NLM Chemicals)
KW  - RNA-Binding Protein EWS (NLM Chemicals)
KW  - Kruppel-Like Transcription Factors (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40413488
DO  - DOI:10.1186/s40478-025-02037-5
UR  - https://inrepo02.dkfz.de/record/301575
ER  -