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@ARTICLE{Okonechnikov:296134,
      author       = {K. Okonechnikov$^*$ and D. R. Ghasemi$^*$ and D.
                      Schrimpf$^*$ and S. Tonn and M. Mynarek and J. Koster and T.
                      Milde$^*$ and T. Zheng$^*$ and P. Sievers$^*$ and F.
                      Sahm$^*$ and D. T. W. Jones$^*$ and A. von Deimling$^*$ and
                      S. M. Pfister$^*$ and M. Kool$^*$ and K. W. Pajtler$^*$ and
                      A. Korshunov$^*$},
      title        = {{B}iglycan-driven risk stratification in {ZFTA}-{RELA}
                      fusion supratentorial ependymomas through transcriptome
                      profiling.},
      journal      = {Acta Neuropathologica Communications},
      volume       = {13},
      number       = {1},
      issn         = {2051-5960},
      address      = {London},
      publisher    = {Biomed Central},
      reportid     = {DKFZ-2025-00064},
      pages        = {4},
      year         = {2025},
      note         = {#EA:B062#LA:B300#},
      abstract     = {Recent genomic studies have allowed the subdivision of
                      intracranial ependymomas into molecularly distinct groups
                      with highly specific clinical features and outcomes. The
                      majority of supratentorial ependymomas (ST-EPN) harbor
                      ZFTA-RELA fusions which were designated, in general, as an
                      intermediate risk tumor variant. However, molecular
                      prognosticators within ST-EPN ZFTA-RELA have not been
                      determined yet. Here, we performed methylation-based DNA
                      profiling and transcriptome RNA sequencing analysis of 80
                      ST-EPN ZFTA-RELA investigating the clinical significance of
                      various molecular patterns. The principal types of ZFTA-RELA
                      fusions, based on breakpoint location, demonstrated no
                      significant correlations with clinical outcomes. Multigene
                      analysis disclosed 1892 survival-associated genes, and a
                      metagene set of 100 genes subdivided ST-EPN ZFTA-RELA into
                      favorable and unfavorable transcriptome subtypes composed of
                      different cell subpopulations as detected by deconvolution
                      analysis. BGN (biglycan) was identified as the top-ranked
                      survival-associated gene and high BGN expression levels were
                      associated with poor survival (Hazard Ratio 17.85 for PFS
                      and 45.48 for OS; log-rank; p-value < 0.01). Furthermore,
                      BGN immunopositivity was identified as a strong prognostic
                      indicator of poor survival in ST-EPN, and this finding was
                      confirmed in an independent validation set of 56 samples.
                      Our results indicate that integrating BGN expression (at
                      mRNA and/or protein level) into risk stratification models
                      may improve ST-EPN ZFTA-RELA outcome prediction. Therefore,
                      gene and/or protein expression analyses for this molecular
                      marker could be adopted for ST-EPN ZFTA-RELA prognostication
                      and may help assign patients to optimal therapies in
                      prospective clinical trials.},
      keywords     = {Humans / Ependymoma: genetics / Ependymoma: metabolism /
                      Ependymoma: pathology / Supratentorial Neoplasms: genetics /
                      Supratentorial Neoplasms: pathology / Supratentorial
                      Neoplasms: metabolism / Male / Female / Gene Expression
                      Profiling: methods / Transcription Factor RelA: genetics /
                      Transcription Factor RelA: metabolism / Adult / Middle Aged
                      / Adolescent / Child / Young Adult / Child, Preschool / Aged
                      / Prognosis / Risk Assessment: methods / Oncogene Proteins,
                      Fusion: genetics / Oncogene Proteins, Fusion: metabolism /
                      BGN (Other) / ZFTA-RELA fusion (Other) / Ependymoma (Other)
                      / Expression (Other) / Prognosis (Other) / Transcription
                      Factor RelA (NLM Chemicals) / RELA protein, human (NLM
                      Chemicals) / Oncogene Proteins, Fusion (NLM Chemicals)},
      cin          = {B062 / HD01 / B300 / B310 / B360},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)B300-20160331 / I:(DE-He78)B310-20160331 /
                      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:39762990},
      doi          = {10.1186/s40478-024-01921-w},
      url          = {https://inrepo02.dkfz.de/record/296134},
}