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@ARTICLE{Sievers:300620,
      author       = {P. Sievers$^*$ and S. Arora and T. Hielscher$^*$ and D.
                      Savran$^*$ and D. Schrimpf$^*$ and R. Banan$^*$ and D.
                      Vonhören$^*$ and S. Pusch$^*$ and M. Sill$^*$ and R. Appay
                      and H.-G. Wirsching and T. Hortobagyi and H. Dohmen and T.
                      Acker and P. Kohlhof-Meinecke and L. Schweizer$^*$ and A. K.
                      Wefers and P. Harter$^*$ and C. Hartmann and R. Beschorner
                      and J. Schittenhelm and F. Behling and G. Tabatabai and C.
                      Mawrin and M. Snuderl and S. L. N. Maas and P. Wesseling and
                      S. Brandner and A. Korshunov$^*$ and M. Ratliff$^*$ and S.
                      M. Krieg and W. Wick$^*$ and D. T. W. Jones$^*$ and S. M.
                      Pfister$^*$ and E. C. Holland and A. von Deimling$^*$ and F.
                      Szulzewsky and F. Sahm$^*$},
      title        = {{M}olecular signatures define {BAP}1-altered meningioma as
                      a distinct {CNS} tumor with deregulation of {P}olycomb
                      repressive complex target genes.},
      journal      = {Neuro-Oncology},
      volume       = {27},
      number       = {9},
      issn         = {1522-8517},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2025-00834},
      pages        = {2326-2340},
      year         = {2025},
      note         = {#EA:B300#LA:B300# / 2025 Oct 14;27(9):2326-2340},
      abstract     = {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.'},
      keywords     = {BAP1 (Other) / Chromosome 3p loss (Other) / Meningioma
                      (Other) / Polycomb signaling (Other) / rhabdoid (Other)},
      cin          = {B300 / C060 / B062 / HD01 / FM01 / MU01 / B320 / B360},
      ddc          = {610},
      cid          = {I:(DE-He78)B300-20160331 / I:(DE-He78)C060-20160331 /
                      I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)FM01-20160331 / I:(DE-He78)MU01-20160331 /
                      I:(DE-He78)B320-20160331 / I:(DE-He78)B360-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40249111},
      doi          = {10.1093/neuonc/noaf105},
      url          = {https://inrepo02.dkfz.de/record/300620},
}