Sievers, Philipp and Arora, Sonali and Hielscher, Thomas and Savran, Dilan and Schrimpf, Daniel and Banan, Rouzbeh and Vonhoeren, David and Pusch, Stefan and Sill, Martin and Appay, Romain and Wirsching, Hans-Georg and Hortobagyi, Tibor and Dohmen, Hildegard and Acker, Till and Kohlhof-Meinecke, Patricia and Schweizer, Leonille and Wefers, Annika K. and Harter, Patrick N. and Hartmann, Christian and Beschorner, Rudi and Schittenhelm, Jens and Behling, Felix and Tabatabai, Ghazaleh and Mawrin, Christian and Snuderl, Matija and Maas, Sybren L. N. and Wesseling, Pieter and Brandner, Sebastian and Korshunov, Andrey and Ratliff, Miriam and Krieg, Sandro M. and Wick, Wolfgang and Jones, David T. W. and Pfister, Stefan M. and Holland, Eric C. and von Deimling, Andreas and Szulzewsky, Frank and Sahm, Felix (2025) Molecular signatures define BAP1-altered meningioma as a distinct CNS tumor with deregulation of Polycomb repressive complex target genes. NEURO-ONCOLOGY, 27 (9). pp. 2326-2340. ISSN 1522-8517, 1523-5866
Full text not available from this repository. (Request a copy)Abstract
Background 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.Methods 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.Results 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.Conclusions 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."
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | METHYLATION-BASED CLASSIFICATION; CENTRAL-NERVOUS-SYSTEM; BAP1 MUTATIONS; GERMLINE; MULTICENTER; H2AK119UB1; FAMILIES; BAP1; chromosome 3p loss; meningioma; polycomb signaling; rhabdoid |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Neuropathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Mar 2026 05:58 |
| Last Modified: | 24 Mar 2026 05:58 |
| URI: | https://pred.uni-regensburg.de/id/eprint/68092 |
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