Glioneuronal tumors PATZ1-fused: clinico-molecular and DNA methylation signatures for a variety of morphological and radiological profiles
Abstract 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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-05-01
|
| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-025-02037-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849730786991800320 |
|---|---|
| author | Arnault Tauziède-Espariat Volodia Dangouloff-Ros Philipp Sievers Mathilde Duchesne Aurore Siegfried Yvan Nicaise Nathalie Boddaert Lauren Hasty Alice Métais Carine Ngo François le Loarer Corinne Bouvier Alix Fontaine Audrey Rousseau Florent Marguet Kévin Beccaria Thomas Blauwblomme Emmanuelle Uro-Coste Pascale Varlet On behalf of the RENOCLIP-LOC |
| author_facet | Arnault Tauziède-Espariat Volodia Dangouloff-Ros Philipp Sievers Mathilde Duchesne Aurore Siegfried Yvan Nicaise Nathalie Boddaert Lauren Hasty Alice Métais Carine Ngo François le Loarer Corinne Bouvier Alix Fontaine Audrey Rousseau Florent Marguet Kévin Beccaria Thomas Blauwblomme Emmanuelle Uro-Coste Pascale Varlet On behalf of the RENOCLIP-LOC |
| author_sort | Arnault Tauziède-Espariat |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-7201afcdf95d45a1b6f8046e1a6ec79c |
| institution | DOAJ |
| issn | 2051-5960 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj-art-7201afcdf95d45a1b6f8046e1a6ec79c2025-08-20T03:08:45ZengBMCActa Neuropathologica Communications2051-59602025-05-0113111210.1186/s40478-025-02037-5Glioneuronal tumors PATZ1-fused: clinico-molecular and DNA methylation signatures for a variety of morphological and radiological profilesArnault Tauziède-Espariat0Volodia Dangouloff-Ros1Philipp Sievers2Mathilde Duchesne3Aurore Siegfried4Yvan Nicaise5Nathalie Boddaert6Lauren Hasty7Alice Métais8Carine Ngo9François le Loarer10Corinne Bouvier11Alix Fontaine12Audrey Rousseau13Florent Marguet14Kévin Beccaria15Thomas Blauwblomme16Emmanuelle Uro-Coste17Pascale Varlet18On behalf of the RENOCLIP-LOCDepartment of Neuropathology, GHU Paris-Psychiatrie et Neurosciences, Sainte-Anne HospitalUniversité de ParisDepartment of Neuropathology, Institute of Pathology, University Hospital HeidelbergDepartment of Pathology, Dupuytren University HospitalDepartment of Pathology, Toulouse University HospitalDepartment of Pathology, Toulouse University HospitalUniversité de ParisDepartment of Neuropathology, GHU Paris-Psychiatrie et Neurosciences, Sainte-Anne HospitalDepartment of Neuropathology, GHU Paris-Psychiatrie et Neurosciences, Sainte-Anne HospitalDepartment of Pathology, Gustave Roussy InstituteDepartment of Biopathology, Institut BergoniéInst Neurophysiopathol, and APHM, Department of Anatomopathology and Neuropathology, Aix-Marseille Univ, CNRS, INP, La Timone HospitalDepartment of Pathology, Angers HospitalDepartment of Pathology, Angers HospitalDepartment of Pathology, Rouen HospitalUniversité de ParisUniversité de ParisDepartment of Pathology, Toulouse University HospitalDepartment of Neuropathology, GHU Paris-Psychiatrie et Neurosciences, Sainte-Anne HospitalAbstract 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.https://doi.org/10.1186/s40478-025-02037-5Glioneuronal tumorEWSR1::PATZ1MN1::PATZ1DNA-methylation |
| spellingShingle | Arnault Tauziède-Espariat Volodia Dangouloff-Ros Philipp Sievers Mathilde Duchesne Aurore Siegfried Yvan Nicaise Nathalie Boddaert Lauren Hasty Alice Métais Carine Ngo François le Loarer Corinne Bouvier Alix Fontaine Audrey Rousseau Florent Marguet Kévin Beccaria Thomas Blauwblomme Emmanuelle Uro-Coste Pascale Varlet On behalf of the RENOCLIP-LOC Glioneuronal tumors PATZ1-fused: clinico-molecular and DNA methylation signatures for a variety of morphological and radiological profiles Acta Neuropathologica Communications Glioneuronal tumor EWSR1::PATZ1 MN1::PATZ1 DNA-methylation |
| title | Glioneuronal tumors PATZ1-fused: clinico-molecular and DNA methylation signatures for a variety of morphological and radiological profiles |
| title_full | Glioneuronal tumors PATZ1-fused: clinico-molecular and DNA methylation signatures for a variety of morphological and radiological profiles |
| title_fullStr | Glioneuronal tumors PATZ1-fused: clinico-molecular and DNA methylation signatures for a variety of morphological and radiological profiles |
| title_full_unstemmed | Glioneuronal tumors PATZ1-fused: clinico-molecular and DNA methylation signatures for a variety of morphological and radiological profiles |
| title_short | Glioneuronal tumors PATZ1-fused: clinico-molecular and DNA methylation signatures for a variety of morphological and radiological profiles |
| title_sort | glioneuronal tumors patz1 fused clinico molecular and dna methylation signatures for a variety of morphological and radiological profiles |
| topic | Glioneuronal tumor EWSR1::PATZ1 MN1::PATZ1 DNA-methylation |
| url | https://doi.org/10.1186/s40478-025-02037-5 |
| work_keys_str_mv | AT arnaulttauziedeespariat glioneuronaltumorspatz1fusedclinicomolecularanddnamethylationsignaturesforavarietyofmorphologicalandradiologicalprofiles AT volodiadangouloffros glioneuronaltumorspatz1fusedclinicomolecularanddnamethylationsignaturesforavarietyofmorphologicalandradiologicalprofiles AT philippsievers glioneuronaltumorspatz1fusedclinicomolecularanddnamethylationsignaturesforavarietyofmorphologicalandradiologicalprofiles AT mathildeduchesne glioneuronaltumorspatz1fusedclinicomolecularanddnamethylationsignaturesforavarietyofmorphologicalandradiologicalprofiles AT auroresiegfried glioneuronaltumorspatz1fusedclinicomolecularanddnamethylationsignaturesforavarietyofmorphologicalandradiologicalprofiles AT yvannicaise glioneuronaltumorspatz1fusedclinicomolecularanddnamethylationsignaturesforavarietyofmorphologicalandradiologicalprofiles AT nathalieboddaert glioneuronaltumorspatz1fusedclinicomolecularanddnamethylationsignaturesforavarietyofmorphologicalandradiologicalprofiles AT laurenhasty glioneuronaltumorspatz1fusedclinicomolecularanddnamethylationsignaturesforavarietyofmorphologicalandradiologicalprofiles AT alicemetais glioneuronaltumorspatz1fusedclinicomolecularanddnamethylationsignaturesforavarietyofmorphologicalandradiologicalprofiles AT carinengo glioneuronaltumorspatz1fusedclinicomolecularanddnamethylationsignaturesforavarietyofmorphologicalandradiologicalprofiles AT francoisleloarer glioneuronaltumorspatz1fusedclinicomolecularanddnamethylationsignaturesforavarietyofmorphologicalandradiologicalprofiles AT corinnebouvier glioneuronaltumorspatz1fusedclinicomolecularanddnamethylationsignaturesforavarietyofmorphologicalandradiologicalprofiles AT alixfontaine glioneuronaltumorspatz1fusedclinicomolecularanddnamethylationsignaturesforavarietyofmorphologicalandradiologicalprofiles AT audreyrousseau glioneuronaltumorspatz1fusedclinicomolecularanddnamethylationsignaturesforavarietyofmorphologicalandradiologicalprofiles AT florentmarguet glioneuronaltumorspatz1fusedclinicomolecularanddnamethylationsignaturesforavarietyofmorphologicalandradiologicalprofiles AT kevinbeccaria glioneuronaltumorspatz1fusedclinicomolecularanddnamethylationsignaturesforavarietyofmorphologicalandradiologicalprofiles AT thomasblauwblomme glioneuronaltumorspatz1fusedclinicomolecularanddnamethylationsignaturesforavarietyofmorphologicalandradiologicalprofiles AT emmanuelleurocoste glioneuronaltumorspatz1fusedclinicomolecularanddnamethylationsignaturesforavarietyofmorphologicalandradiologicalprofiles AT pascalevarlet glioneuronaltumorspatz1fusedclinicomolecularanddnamethylationsignaturesforavarietyofmorphologicalandradiologicalprofiles AT onbehalfoftherenocliploc glioneuronaltumorspatz1fusedclinicomolecularanddnamethylationsignaturesforavarietyofmorphologicalandradiologicalprofiles |