ATRX loss in adult gliomas lacking H3 alterations or IDH mutations, an exceptional situation for exceptional diagnoses: the experience of Sainte-Anne hospital
Year: 2025
Type: article
Abstract: ATRX immunostaining constitutes a routinely used biomarker for the practice of neuropathology. The loss of ATRX expression correlating with ATRX gene alterations is implicated in a wide variety of pediatric and adult gliomas, and has been indexed as a desirable or essential diagnostic criterion for four tumor types featured in the latest world health organization classification of central nervous system Tumors. In adult-type diffuse glioma, the loss of ATRX expression is a hallmark of astrocytoma, IDH-mutant. Recently, novel tumor types and alterations have been referenced in the literature. These include the high-grade astrocytoma with piloid features (HGAP), for which no consistent clinicopathological features have been defined, and the presence of other alterations in the Krebs cycle genes (variants of the Fumarate hydratase -FH- gene) found in gliomas resembling astrocytomas, IDH-mutant. Because of this rapidly evolving classification and histomolecular landscape, we retrospectively analyzed adult gliomas diagnosed over a four consecutive year period to identify supratentorial gliomas, lacking H3 alterations or IDH mutations and harboring a loss of ATRX expression, in order to update their diagnoses in terms of histopathology, genetics and epigenetics. Four specimens (from 620 adult gliomas, 0.7%) were reclassified at the end of the molecular workup, as: 1/ one HGAP, 2/ one malignant transformation with a primitive neuronal component of an astrocytoma, IDH-mutant which lost the IDH2 mutation at recurrence, 3/ a glioma, FH-mutant for which the histopathological and epigenetic features were similar to an astrocytoma, IDH-mutant, and 4/ a glioblastoma, IDH-wildtype. To conclude, these exceptional cases extend the spectrum of ATRX loss in gliomas, beyond the astrocytoma, IDH-mutant and the diffuse hemispheric glioma, H3 G34-mutant.
Institutions: Inserm, Université Paris Cité, Centre Hospitalier Sainte-Anne, Institut de Psychiatrie et Neurosciences de Paris, GHU Paris psychiatrie & neurosciences, Centre Hospitalier Universitaire Henri-Mondor, Hôpitaux Universitaires Henri-Mondor, German Cancer Research Center, University of California, San Francisco, Heidelberg University, University Hospital Heidelberg, Deutsches Konsortium für Translationale Krebsforschung, Institut Curie, Hôpital Paul-Brousse, Hôpital Bichat-Claude-Bernard
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,790
OpenAlex ID: W4411282802