Acta Neuropathologica Communications (Apr 2024)
CNS tumors with PLAGL1-fusion: beyond ZFTA and YAP1 in the genetic spectrum of supratentorial ependymomas
- Arnault Tauziède-Espariat,
- Yvan Nicaise,
- Philipp Sievers,
- Felix Sahm,
- Andreas von Deimling,
- Delphine Guillemot,
- Gaëlle Pierron,
- Mathilde Duchesne,
- Myriam Edjlali,
- Volodia Dangouloff-Ros,
- Nathalie Boddaert,
- Alexandre Roux,
- Edouard Dezamis,
- Lauren Hasty,
- Benoît Lhermitte,
- Edouard Hirsch,
- Maria Paola Valenti Hirsch,
- François-Daniel Ardellier,
- Mélodie-Anne Karnoub,
- Marie Csanyi,
- Claude-Alain Maurage,
- Karima Mokhtari,
- Franck Bielle,
- Valérie Rigau,
- Thomas Roujeau,
- Marine Abad,
- Sébastien Klein,
- Michèle Bernier,
- Catherine Horodyckid,
- Clovis Adam,
- Petter Brandal,
- Pitt Niehusmann,
- Quentin Vannod-Michel,
- Corentin Provost,
- Nicolas Menjot de Champfleur,
- Lucia Nichelli,
- Alice Métais,
- Cassandra Mariet,
- Fabrice Chrétien,
- Thomas Blauwblomme,
- Kévin Beccaria,
- Johan Pallud,
- Stéphanie Puget,
- Emmanuelle Uro-Coste,
- Pascale Varlet,
- RENOCLIP-LOC
Affiliations
- Arnault Tauziède-Espariat
- Department of Neuropathology, GHU Paris-Psychiatrie Et Neurosciences, Sainte-Anne Hospital
- Yvan Nicaise
- Department of Pathology, Toulouse University Hospital
- Philipp Sievers
- Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg
- Felix Sahm
- Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg
- Andreas von Deimling
- Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg
- Delphine Guillemot
- Paris-Sciences-Lettres, Curie Institute Research Center
- Gaëlle Pierron
- Paris-Sciences-Lettres, Curie Institute Research Center
- Mathilde Duchesne
- Department of Pathology, Dupuytren University Hospital
- Myriam Edjlali
- Radiology Department, AP-HP, Raymond Poincaré Hospital
- Volodia Dangouloff-Ros
- Pediatric Radiology Department, AP-HP, Hôpital Universitaire Necker-Enfants Malades, France, and Université de Paris, INSERM ERL UA10, INSERM U1163, Institut Imagine
- Nathalie Boddaert
- Pediatric Radiology Department, AP-HP, Hôpital Universitaire Necker-Enfants Malades, France, and Université de Paris, INSERM ERL UA10, INSERM U1163, Institut Imagine
- Alexandre Roux
- Department of Neurosurgery, GHU Paris-Psychiatrie Et Neurosciences, Sainte-Anne Hospital
- Edouard Dezamis
- Department of Neurosurgery, GHU Paris-Psychiatrie Et Neurosciences, Sainte-Anne Hospital
- Lauren Hasty
- Department of Neuropathology, GHU Paris-Psychiatrie Et Neurosciences, Sainte-Anne Hospital
- Benoît Lhermitte
- Department of Pathology, Strasbourg Hospital
- Edouard Hirsch
- Department of Neurology, Strasbourg Hospital
- Maria Paola Valenti Hirsch
- Radiology 2 Department, Strasbourg University Hospital, Hautepierre Hospital
- François-Daniel Ardellier
- Radiology 2 Department, Strasbourg University Hospital, Hautepierre Hospital
- Mélodie-Anne Karnoub
- Department of Pediatric Neurosurgery, Lille University Hospital
- Marie Csanyi
- Institute of Pathology, Centre de Biologie Pathologie, Lille University Hospital
- Claude-Alain Maurage
- Institute of Pathology, Centre de Biologie Pathologie, Lille University Hospital
- Karima Mokhtari
- Sorbonne Université, AP-HP, Institut du Cerveau - Paris Brain Institute - ICM, Inserm,, CNRS, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix
- Franck Bielle
- Sorbonne Université, AP-HP, Institut du Cerveau - Paris Brain Institute - ICM, Inserm,, CNRS, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix
- Valérie Rigau
- Department of Pathology, Gui de Chauliac Hospital
- Thomas Roujeau
- Department of Neurosurgery, Gui de Chauliac Hospital
- Marine Abad
- Department of Pathology, Jean Minjoz Hospital
- Sébastien Klein
- Department of Pediatric Oncology, Jean Minjoz Hospital
- Michèle Bernier
- Department of Pathology, Foch Hospital
- Catherine Horodyckid
- Department of Neurosurgery, Foch Hospital
- Clovis Adam
- Department of Pathology, Bicêtre Hospital
- Petter Brandal
- Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, Oslo University Hospital
- Pitt Niehusmann
- Devision of Cancer Medicine, Oslo University Hospital
- Quentin Vannod-Michel
- Radiology Department, Lille University Hospital
- Corentin Provost
- Department of Radiology, GHU-Paris-Psychiatrie Et Neurosciences, Hôpital Sainte Anne
- Nicolas Menjot de Champfleur
- Department of Radiology, Gui de Chauliac Hospital
- Lucia Nichelli
- Department of Neuroradiology, Sorbonne Université, AP-HP, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix
- Alice Métais
- Department of Neuropathology, GHU Paris-Psychiatrie Et Neurosciences, Sainte-Anne Hospital
- Cassandra Mariet
- Department of Neuropathology, GHU Paris-Psychiatrie Et Neurosciences, Sainte-Anne Hospital
- Fabrice Chrétien
- Department of Neuropathology, GHU Paris-Psychiatrie Et Neurosciences, Sainte-Anne Hospital
- Thomas Blauwblomme
- Department of Pediatric Neurosurgery, Necker Hospital, APHP, Université Paris Descartes, Sorbonne Paris Cité
- Kévin Beccaria
- Department of Pediatric Neurosurgery, Necker Hospital, APHP, Université Paris Descartes, Sorbonne Paris Cité
- Johan Pallud
- Department of Neurosurgery, GHU Paris-Psychiatrie Et Neurosciences, Sainte-Anne Hospital
- Stéphanie Puget
- Department of Neurosurgery, La Martinique Hospital
- Emmanuelle Uro-Coste
- Department of Pathology, Toulouse University Hospital
- Pascale Varlet
- Department of Neuropathology, GHU Paris-Psychiatrie Et Neurosciences, Sainte-Anne Hospital
- RENOCLIP-LOC
- DOI
- https://doi.org/10.1186/s40478-023-01695-7
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 14
Abstract
Abstract A novel methylation class, “neuroepithelial tumor, with PLAGL1 fusion” (NET-PLAGL1), has recently been described, based on epigenetic features, as a supratentorial pediatric brain tumor with recurrent histopathological features suggesting an ependymal differentiation. Because of the recent identification of this neoplastic entity, few histopathological, radiological and clinical data are available. Herein, we present a detailed series of nine cases of PLAGL1-fused supratentorial tumors, reclassified from a series of supratentorial ependymomas, non-ZFTA/non-YAP1 fusion-positive and subependymomas of the young. This study included extensive clinical, radiological, histopathological, ultrastructural, immunohistochemical, genetic and epigenetic (DNA methylation profiling) data for characterization. An important aim of this work was to evaluate the sensitivity and specificity of a novel fluorescent in situ hybridization (FISH) targeting the PLAGL1 gene. Using histopathology, immunohistochemistry and electron microscopy, we confirmed the ependymal differentiation of this new neoplastic entity. Indeed, the cases histopathologically presented as “mixed subependymomas-ependymomas” with well-circumscribed tumors exhibiting a diffuse immunoreactivity for GFAP, without expression of Olig2 or SOX10. Ultrastructurally, they also harbored features reminiscent of ependymal differentiation, such as cilia. Different gene partners were fused with PLAGL1: FOXO1, EWSR1 and for the first time MAML2. The PLAGL1 FISH presented a 100% sensitivity and specificity according to RNA sequencing and DNA methylation profiling results. This cohort of supratentorial PLAGL1-fused tumors highlights: 1/ the ependymal cell origin of this new neoplastic entity; 2/ benefit of looking for a PLAGL1 fusion in supratentorial cases of non-ZFTA/non-YAP1 ependymomas; and 3/ the usefulness of PLAGL1 FISH.
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