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ATRX loss in adult gliomas lacking H3 alterations or IDH mutations, an exceptional situation for exceptional diagnoses: the experience of Sainte-Anne hospital
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ATRX loss in adult gliomas lacking H3 alterations or IDH mutations, an exceptional situation for exceptional diagnoses: the experience of Sainte-Anne hospital
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ATRX loss in adult gliomas lacking H3 alterations or IDH mutations, an exceptional situation for exceptional diagnoses: the experience of Sainte-Anne hospital
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Journal Article
ATRX loss in adult gliomas lacking H3 alterations or IDH mutations, an exceptional situation for exceptional diagnoses: the experience of Sainte-Anne hospital
2025
Overview
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.
Publisher
BioMed Central,BioMed Central Ltd,Nature Publishing Group,BMC
Subject
/ Adults
/ Aged
/ ATRX
/ Biomedical and Life Sciences
/ Biopsy
/ Brain Neoplasms - metabolism
/ Cloning
/ Female
/ Genes
/ Genomes
/ Glioma
/ Gliomas
/ HGAP
/ Humans
/ Isocitrate Dehydrogenase - genetics
/ Kinases
/ Male
/ Mutation
/ Proteins
/ Software
/ Tumors
/ X-linked Nuclear Protein - genetics
