TY  - JOUR
AU  - Sievers, Philipp
AU  - Arora, Sonali
AU  - Hielscher, Thomas
AU  - Savran, Dilan
AU  - Schrimpf, Daniel
AU  - Banan, Rouzbeh
AU  - Vonhören, David
AU  - Pusch, Stefan
AU  - Sill, Martin
AU  - Appay, Romain
AU  - Wirsching, Hans-Georg
AU  - Hortobagyi, Tibor
AU  - Dohmen, Hildegard
AU  - Acker, Till
AU  - Kohlhof-Meinecke, Patricia
AU  - Schweizer, Leonille
AU  - Wefers, Annika K
AU  - Harter, Patrick
AU  - Hartmann, Christian
AU  - Beschorner, Rudi
AU  - Schittenhelm, Jens
AU  - Behling, Felix
AU  - Tabatabai, Ghazaleh
AU  - Mawrin, Christian
AU  - Snuderl, Matija
AU  - Maas, Sybren L N
AU  - Wesseling, Pieter
AU  - Brandner, Sebastian
AU  - Korshunov, Andrey
AU  - Ratliff, Miriam
AU  - Krieg, Sandro M
AU  - Wick, Wolfgang
AU  - Jones, David T W
AU  - Pfister, Stefan M
AU  - Holland, Eric C
AU  - von Deimling, Andreas
AU  - Szulzewsky, Frank
AU  - Sahm, Felix
TI  - Molecular signatures define BAP1-altered meningioma as a distinct CNS tumor with deregulation of Polycomb repressive complex target genes.
JO  - Neuro-Oncology
VL  - 27
IS  - 9
SN  - 1522-8517
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DKFZ-2025-00834
SP  - 2326-2340
PY  - 2025
N1  - #EA:B300#LA:B300# / 2025 Oct 14;27(9):2326-2340
AB  - 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
KW  - BAP1 (Other)
KW  - Chromosome 3p loss (Other)
KW  - Meningioma (Other)
KW  - Polycomb signaling (Other)
KW  - rhabdoid (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40249111
DO  - DOI:10.1093/neuonc/noaf105
UR  - https://inrepo02.dkfz.de/record/300620
ER  -