Buchumschlag

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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Sievers, Philipp (VerfasserIn) , Arora, Sonali (VerfasserIn) , Hielscher, Thomas (VerfasserIn) , Savran, Dilan (VerfasserIn) , Schrimpf, Daniel (VerfasserIn) , Banan, Rouzbeh (VerfasserIn) , Vonhören, David (VerfasserIn) , Pusch, Stefan (VerfasserIn) , Sill, Martin (VerfasserIn) , Appay, Romain (VerfasserIn) , Wirsching, Hans-Georg (VerfasserIn) , Hortobagyi, Tibor (VerfasserIn) , Dohmen, Hildegard (VerfasserIn) , Acker, Till (VerfasserIn) , Kohlhof-Meinecke, Patricia (VerfasserIn) , Schweizer, Leonille (VerfasserIn) , Wefers, Annika K. (VerfasserIn) , Harter, Patrick Nikolaus (VerfasserIn) , Hartmann, Christian (VerfasserIn) , Beschorner, Rudi (VerfasserIn) , Schittenhelm, Jens Florian (VerfasserIn) , Behling, Felix (VerfasserIn) , Tabatabai, Ghazaleh (VerfasserIn) , Mawrin, Christian (VerfasserIn) , Snuderl, Matija (VerfasserIn) , Maas, Sybren L. N. (VerfasserIn) , Wesseling, Pieter (VerfasserIn) , Brandner, Sebastian (VerfasserIn) , Korshunov, Andrey (VerfasserIn) , Ratliff, Miriam (VerfasserIn) , Krieg, Sandro (VerfasserIn) , Wick, Wolfgang (VerfasserIn) , Jones, David T. W. (VerfasserIn) , Pfister, Stefan (VerfasserIn) , Holland, Eric C (VerfasserIn) , Deimling, Andreas von (VerfasserIn) , Szulzewsky, Frank (VerfasserIn) , Sahm, Felix (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: September 2025
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
Volltext
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
Beschreibung
Zusammenfassung: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.”
Beschreibung:Online veröffentlicht: 18. April 2025
Gesehen am 22.10.2025
Beschreibung:Online Resource
ISSN:1523-5866
DOI:10.1093/neuonc/noaf105

Ähnliche Einträge