Pleomorphic xanthoastrocytoma is a heterogeneous entity with pTERT mutations prognosticating shorter survival
Pleomorphic xanthoastrocytoma (PXA) in its classic manifestation exhibits distinct morphological features and is assigned to CNS WHO grade 2 or grade 3. Distinction from glioblastoma variants and lower grade glial and glioneuronal tumors is a common diagnostic challenge. We compared a morphologicall...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
Jan 10 2022
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| In: |
Acta Neuropathologica Communications
Year: 2022, Volume: 10, Pages: 1-10 |
| ISSN: | 2051-5960 |
| DOI: | 10.1186/s40478-021-01308-1 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1186/s40478-021-01308-1
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| Author Notes: | Azadeh Ebrahimi, Andrey Korshunov, Guido Reifenberger, David Capper, Joerg Felsberg, Elena Trisolini, Bianca Pollo, Chiara Calatozzolo, Marco Prinz, Ori Staszewski, Leonille Schweizer, Jens Schittenhelm, Patrick N. Harter, Werner Paulus, Christian Thomas, Patricia Kohlhof-Meinecke, Marcel Seiz-Rosenhagen, Till Milde, Belén M. Casalini, Abigail Suwala, Annika K. Wefers, Annekathrin Reinhardt, Philipp Sievers, Christof M. Kramm, Nima Etminam, Andreas Unterberg, Wolfgang Wick, Christel Herold-Mende, Dominik Sturm, Stefan M. Pfister, Martin Sill, David T.W. Jones, Daniel Schrimpf, David E. Reuss, Ken Aldape, Zied Abdullaev, Felix Sahm, Andreas von Deimling and Damian Stichel |
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| 245 | 1 | 0 | |a Pleomorphic xanthoastrocytoma is a heterogeneous entity with pTERT mutations prognosticating shorter survival |c Azadeh Ebrahimi, Andrey Korshunov, Guido Reifenberger, David Capper, Joerg Felsberg, Elena Trisolini, Bianca Pollo, Chiara Calatozzolo, Marco Prinz, Ori Staszewski, Leonille Schweizer, Jens Schittenhelm, Patrick N. Harter, Werner Paulus, Christian Thomas, Patricia Kohlhof-Meinecke, Marcel Seiz-Rosenhagen, Till Milde, Belén M. Casalini, Abigail Suwala, Annika K. Wefers, Annekathrin Reinhardt, Philipp Sievers, Christof M. Kramm, Nima Etminam, Andreas Unterberg, Wolfgang Wick, Christel Herold-Mende, Dominik Sturm, Stefan M. Pfister, Martin Sill, David T.W. Jones, Daniel Schrimpf, David E. Reuss, Ken Aldape, Zied Abdullaev, Felix Sahm, Andreas von Deimling and Damian Stichel |
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| 520 | |a Pleomorphic xanthoastrocytoma (PXA) in its classic manifestation exhibits distinct morphological features and is assigned to CNS WHO grade 2 or grade 3. Distinction from glioblastoma variants and lower grade glial and glioneuronal tumors is a common diagnostic challenge. We compared a morphologically defined set of PXA (histPXA) with an independent set, defined by DNA methylation analysis (mcPXA). HistPXA encompassed 144 tumors all subjected to DNA methylation array analysis. Sixty-two histPXA matched to the methylation class mcPXA. These were combined with the cases that showed the mcPXA signature but had received a histopathological diagnosis other than PXA. This cohort constituted a set of 220 mcPXA. Molecular and clinical parameters were analyzed in these groups. Morphological parameters were analyzed in a subset of tumors with FFPE tissue available. HistPXA revealed considerable heterogeneity in regard to methylation classes, with methylation classes glioblastoma and ganglioglioma being the most frequent mismatches. Similarly, the mcPXA cohort contained tumors of diverse histological diagnoses, with glioblastoma constituting the most frequent mismatch. Subsequent analyses demonstrated the presence of canonical pTERT mutations to be associated with unfavorable prognosis among mcPXA. Based on these data, we consider the tumor type PXA to be histologically more varied than previously assumed. Histological approach to diagnosis will predominantly identify cases with the established archetypical morphology. DNA methylation analysis includes additional tumors in the tumor class PXA that share similar DNA methylation profile but lack the typical morphology of a PXA. DNA methylation analysis also assist in separating other tumor types with morphologic overlap to PXA. Our data suggest the presence of canonical pTERT mutations as a robust indicator for poor prognosis in methylation class PXA. | ||
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| 650 | 4 | |a Pleomorphic xanthoastrocytoma | |
| 650 | 4 | |a pTERT mutation | |
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