Molecular signatures define BAP1-altered meningioma as a distinct CNS tumor with deregulation of Polycomb repressive complex target genes
Meningiomas are the most common primary intracranial neoplasms, with highly variable patient outcomes. While most meningiomas are benign, a significant subset recurs postoperatively, presenting substantial treatment challenges. BAP1 gene inactivation has been suggested as a marker for aggressive men...
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
September 2025
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| In: |
Neuro-Oncology
Year: 2025, Jahrgang: 27, Heft: 9, Pages: 2326-2340 |
| ISSN: | 1523-5866 |
| DOI: | 10.1093/neuonc/noaf105 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/neuonc/noaf105 Verlag, lizenzpflichtig, Volltext: https://academic.oup.com/neuro-oncology/article/27/9/2326/8116004 
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| Verfasserangaben: | Philipp Sievers, Sonali Arora, Thomas Hielscher, Dilan Savran, Daniel Schrimpf, Rouzbeh Banan, David Vonhören, Stefan Pusch, Martin Sill, Romain Appay, Hans-Georg Wirsching, Tibor Hortobagyi, Hildegard Dohmen, Till Acker, Patricia Kohlhof-Meinecke, Leonille Schweizer, Annika K Wefers, Patrick N Harter, Christian Hartmann, Rudi Beschorner, Jens Schittenhelm, Felix Behling, Ghazaleh Tabatabai, Christian Mawrin, Matija Snuderl, Sybren L N Maas, Pieter Wesseling, Sebastian Brandner, Andrey Korshunov, Miriam Ratliff, Sandro M Krieg, Wolfgang Wick, David T W Jones, Stefan M Pfister, Eric C Holland, Andreas von Deimling, Frank Szulzewsky, Felix Sahm |
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| 245 | 1 | 0 | |a Molecular signatures define BAP1-altered meningioma as a distinct CNS tumor with deregulation of Polycomb repressive complex target genes |c Philipp Sievers, Sonali Arora, Thomas Hielscher, Dilan Savran, Daniel Schrimpf, Rouzbeh Banan, David Vonhören, Stefan Pusch, Martin Sill, Romain Appay, Hans-Georg Wirsching, Tibor Hortobagyi, Hildegard Dohmen, Till Acker, Patricia Kohlhof-Meinecke, Leonille Schweizer, Annika K Wefers, Patrick N Harter, Christian Hartmann, Rudi Beschorner, Jens Schittenhelm, Felix Behling, Ghazaleh Tabatabai, Christian Mawrin, Matija Snuderl, Sybren L N Maas, Pieter Wesseling, Sebastian Brandner, Andrey Korshunov, Miriam Ratliff, Sandro M Krieg, Wolfgang Wick, David T W Jones, Stefan M Pfister, Eric C Holland, Andreas von Deimling, Frank Szulzewsky, Felix Sahm |
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| 520 | |a Meningiomas are the most common primary intracranial neoplasms, with highly variable patient outcomes. While most meningiomas are benign, a significant subset recurs postoperatively, presenting substantial treatment challenges. BAP1 gene inactivation has been suggested as a marker for aggressive meningiomas, although its precise molecular and clinical roles remain poorly understood.To comprehensively investigate BAP1-altered meningiomas, we used six meningiomas with known BAP1 alterations as a discovery set. Genome-wide DNA methylation profiling of these samples, along 11 151 reference meningiomas, identified a distinct molecular cluster (n = 42) using unsupervised visualization approaches. These tumors were further characterized by DNA/RNA sequencing, histopathological examination, and a retrospective review of clinical data, compared to reference meningioma cohorts, providing a thorough characterization of this rare tumor subtype.Our integrative analysis revealed BAP1-altered meningiomas as a distinct CNS tumor subtype, characterized by recurrent loss of chromosome 3p21 and driven by various BAP1-inactivating alterations. Although rhabdoid morphology is present in some cases, it is not exclusive and should not be used as a grading criterion. Progression-free survival analysis showed a median of 21 months (95% CI: 12-NA), with a 2-year overall survival rate of 79% (95% CI: 60%-100%), highlighting the aggressive nature of these tumors. Gene expression profiling revealed upregulation of PRC target genes, dysregulated Polycomb signaling, and elevated expression in several cellular and growth factor pathways.BAP1-altered meningiomas represent a distinct and aggressive CNS tumor subtype associated with PRC dysregulation and recurrent 3p chromosome loss. These findings support the designation “meningioma, BAP1-altered.” | ||
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