Supratentorial non-RELA, ZFTA-fused ependymomas: a comprehensive phenotype genotype correlation highlighting the number of zinc fingers in ZFTA-NCOA1/2 fusions - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Acta Neuropathologica Communications Année : 2021

Supratentorial non-RELA, ZFTA-fused ependymomas: a comprehensive phenotype genotype correlation highlighting the number of zinc fingers in ZFTA-NCOA1/2 fusions

Chiara Benevello
  • Fonction : Auteur
Nathalie Boddaert
  • Fonction : Auteur
Raphaël Saffroy
  • Fonction : Auteur
Lauren Hasty
  • Fonction : Auteur
Ellen Wahler
  • Fonction : Auteur
Mélanie Pagès
  • Fonction : Auteur
Felipe Andreiuolo
  • Fonction : Auteur
Emmanuèle Lechapt
  • Fonction : Auteur
Fabrice Chrétien
  • Fonction : Auteur
Thomas Blauwblomme
  • Fonction : Auteur
Kévin Beccaria
  • Fonction : Auteur
Johan Pallud
  • Fonction : Auteur
Stéphanie Puget
  • Fonction : Auteur
Emmanuelle Uro-Coste
  • Fonction : Auteur
Pascale Varlet
  • Fonction : Auteur

Résumé

Abstract The cIMPACT-NOW Update 7 has replaced the WHO nosology of “ependymoma, RELA fusion positive” by “Supratentorial-ependymoma, C11orf95 -fusion positive”. This modification reinforces the idea that supratentorial-ependymomas exhibiting fusion that implicates the C11orf95 (now called ZFTA ) gene with or without the RELA gene, represent the same histomolecular entity. A hot off the press molecular study has identified distinct clusters of the DNA methylation class of ZFTA fusion-positive tumors. Interestingly, clusters 2 and 4 comprised tumors of different morphologies, with various ZFTA fusions without involvement of RELA. In this paper, we present a detailed series of thirteen cases of non- RELA ZFTA -fused supratentorial tumors with extensive clinical, radiological, histopathological, immunohistochemical, genetic and epigenetic (DNA methylation profiling) characterization. Contrary to the age of onset and MRI aspects similar to RELA fusion-positive EPN, we noted significant histopathological heterogeneity (pleomorphic xanthoastrocytoma-like, astroblastoma-like, ependymoma-like, and even sarcoma-like patterns) in this cohort. Immunophenotypically, these NFκB immunonegative tumors expressed GFAP variably, but EMA constantly and L1CAM frequently. Different gene partners were fused with ZFTA : NCOA1/2 , MAML2 and for the first time MN1 . These tumors had epigenetic homologies within the DNA methylation class of ependymomas-RELA and were classified as satellite clusters 2 and 4. Cluster 2 (n = 9) corresponded to tumors with classic ependymal histological features (n = 4) but also had astroblastic features (n = 5). Various types of ZFTA fusions were associated with cluster 2, but as in the original report, ZFTA:MAML2 fusion was frequent. Cluster 4 was enriched with sarcoma-like tumors. Moreover, we reported a novel anatomy of three ZFTA:NCOA1/2 fusions with only 1 ZFTA zinc finger domain in the putative fusion protein, whereas all previously reported non- RELA ZFTA fusions have 4 ZFTA zinc fingers. All three cases presented a sarcoma-like morphology. This genotype/phenotype association requires further studies for confirmation. Our series is the first to extensively characterize this new subset of supratentorial ZFTA -fused ependymomas and highlights the usefulness of ZFTA FISH analysis to confirm the existence of a rearrangement without RELA abnormality.

Dates et versions

hal-04493324 , version 1 (07-03-2024)

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Arnault Tauziède-Espariat, Aurore Siegfried, Yvan Nicaise, Thomas Kergrohen, Philipp Sievers, et al.. Supratentorial non-RELA, ZFTA-fused ependymomas: a comprehensive phenotype genotype correlation highlighting the number of zinc fingers in ZFTA-NCOA1/2 fusions. Acta Neuropathologica Communications, 2021, 9 (1), pp.135. ⟨10.1186/s40478-021-01238-y⟩. ⟨hal-04493324⟩
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