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@ARTICLE{Chapman:274243,
      author       = {R. J. Chapman and D. R. Ghasemi$^*$ and F. Andreiuolo and
                      V. Zschernack and A. Tauziede Espariat and F. R. Buttarelli
                      and F. Giangaspero and J. Grill and C. Haberler and S. M. L.
                      Paine and I. Scott and T. S. Jacques and M. Sill and S.
                      Pfister$^*$ and J.-P. Kilday and P. Leblond and M. Massimino
                      and H. Witt$^*$ and P. Modena and P. Varlet and T. Pietsch
                      and R. G. Grundy and K. Pajtler$^*$ and T. A. Ritzmann and
                      B. o. E. i. Childhood},
      collaboration = {Adolescence},
      title        = {{O}ptimising biomarkers for accurate ependymoma diagnosis,
                      prognostication and stratification within {I}nternational
                      {C}linical {T}rials: {A} {BIOMECA} study.},
      journal      = {Neuro-Oncology},
      volume       = {25},
      number       = {10},
      issn         = {1522-8517},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2023-00529},
      pages        = {1871-1882},
      year         = {2023},
      note         = {#LA:B062# / 2023 Oct 3;25(10):1871-1882},
      abstract     = {Accurate identification of brain tumour molecular subgroups
                      is increasingly important. We aimed to establish the most
                      accurate and reproducible ependymoma subgroup biomarker
                      detection techniques, across 147 cases from International
                      Society of Pediatric Oncology (SIOP) Ependymoma II trial
                      participants, enrolled in the pan-European 'Biomarkers of
                      Ependymoma in Children and Adolescents (BIOMECA)'
                      study.Across six European BIOMECA laboratories we evaluated
                      epigenetic profiling (DNA methylation array);
                      immunohistochemistry (IHC) for nuclear p65-RELA, H3K27me3,
                      and Tenascin-C; copy number analysis via FISH and MLPA (1q,
                      CDKN2A), and MIP and DNA methylation array (genome-wide copy
                      number evaluation); analysis of ZFTA- and YAP1-fusions by
                      RT-PCR and sequencing, Nanostring and break-apart FISH.DNA
                      Methylation profiling classified $65.3\%$ (n=96/147) of
                      cases as EPN-PFA and $15\%$ (n=22/147) as ST-ZFTA
                      fusion-positive. Immunohistochemical loss of H3K27me3 was a
                      reproducible and accurate surrogate marker for EPN-PFA
                      (sensitivity $99-100\%$ across three centres). IHC for
                      p65-RELA, FISH, and RNA-based analyses effectively
                      identified ZFTA- and YAP1- fused supratentorial ependymomas.
                      Detection of 1q gain using FISH exhibited only $57\%$
                      inter-centre concordance and low sensitivity and specificity
                      whilst MIP, MLPA and DNA methylation-based approaches
                      demonstrated greater accuracy.We confirm, in a prospective
                      trial cohort, that H3K27me3 immunohistochemistry is a robust
                      EPN-PFA biomarker. Tenascin-C should be abandoned as a PFA
                      marker. DNA methylation and MIP arrays are effective tools
                      for copy number analysis of 1q gain, 6q and CDKN2A loss
                      whilst FISH is inadequate. Fusion detection was successful,
                      but rare novel fusions need more extensive technologies.
                      Finally, we propose test sets to guide future diagnostic
                      approaches.},
      keywords     = {Ependymoma (Other) / biomarkers (Other) / brain tumours
                      (Other) / neuro-oncology (Other) / paediatric (Other)},
      cin          = {B062 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36916248},
      doi          = {10.1093/neuonc/noad055},
      url          = {https://inrepo02.dkfz.de/record/274243},
}