%0 Journal Article
%A Sievers, Philipp
%A Arora, Sonali
%A Hielscher, Thomas
%A Savran, Dilan
%A Schrimpf, Daniel
%A Banan, Rouzbeh
%A Vonhören, David
%A Pusch, Stefan
%A Sill, Martin
%A Appay, Romain
%A Wirsching, Hans-Georg
%A Hortobagyi, Tibor
%A Dohmen, Hildegard
%A Acker, Till
%A Kohlhof-Meinecke, Patricia
%A Schweizer, Leonille
%A Wefers, Annika K
%A Harter, Patrick
%A Hartmann, Christian
%A Beschorner, Rudi
%A Schittenhelm, Jens
%A Behling, Felix
%A Tabatabai, Ghazaleh
%A Mawrin, Christian
%A Snuderl, Matija
%A Maas, Sybren L N
%A Wesseling, Pieter
%A Brandner, Sebastian
%A Korshunov, Andrey
%A Ratliff, Miriam
%A Krieg, Sandro M
%A Wick, Wolfgang
%A Jones, David T W
%A Pfister, Stefan M
%A Holland, Eric C
%A von Deimling, Andreas
%A Szulzewsky, Frank
%A Sahm, Felix
%T Molecular signatures define BAP1-altered meningioma as a distinct CNS tumor with deregulation of Polycomb repressive complex target genes.
%J Neuro-Oncology
%V 27
%N 9
%@ 1522-8517
%C Oxford
%I Oxford Univ. Press
%M DKFZ-2025-00834
%P 2326-2340
%D 2025
%Z #EA:B300#LA:B300# / 2025 Oct 14;27(9):2326-2340
%X 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
%K BAP1 (Other)
%K Chromosome 3p loss (Other)
%K Meningioma (Other)
%K Polycomb signaling (Other)
%K rhabdoid (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40249111
%R 10.1093/neuonc/noaf105
%U https://inrepo02.dkfz.de/record/300620