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@ARTICLE{Pohl:287282,
      author       = {L. C. Pohl and M. Leitheiser and D. Obrecht and L.
                      Schweizer$^*$ and A. K. Wefers and A. Eckhardt and M.
                      Raffeld and D. Sturm$^*$ and K. W. Pajtler$^*$ and S.
                      Rutkowski and K. Fukuoka and K. Ichimura and M. Bockmayr and
                      U. Schüller},
      title        = {{M}olecular characteristics and improved survival
                      prediction in a cohort of 2023 ependymomas.},
      journal      = {Acta neuropathologica},
      volume       = {147},
      number       = {1},
      issn         = {0001-6322},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DKFZ-2024-00207},
      pages        = {24},
      year         = {2024},
      abstract     = {The diagnosis of ependymoma has moved from a purely
                      histopathological review with limited prognostic value to an
                      integrated diagnosis, relying heavily on molecular
                      information. However, as the integrated approach is still
                      novel and some molecular ependymoma subtypes are quite rare,
                      few studies have correlated integrated pathology and
                      clinical outcome, often focusing on small series of single
                      molecular types. We collected data from 2023 ependymomas as
                      classified by DNA methylation profiling, consisting of 1736
                      previously published and 287 unpublished methylation
                      profiles. Methylation data and clinical information were
                      correlated, and an integrated model was developed to predict
                      progression-free survival. Patients with EPN-PFA, EPN-ZFTA,
                      and EPN-MYCN tumors showed the worst outcome with 10-year
                      overall survival rates of $56\%,$ $62\%,$ and $32\%,$
                      respectively. EPN-PFA harbored chromosome 1q gains and/or 6q
                      losses as markers for worse survival. In supratentorial
                      EPN-ZFTA, a combined loss of CDKN2A and B indicated worse
                      survival, whereas a single loss did not. Twelve out of 200
                      EPN-ZFTA $(6\%)$ were located in the posterior fossa, and
                      these tumors relapsed or progressed even earlier than
                      supratentorial tumors with a combined loss of CDKN2A/B.
                      Patients with MPE and PF-SE, generally regarded as
                      non-aggressive tumors, only had a 10-year progression-free
                      survival of $59\%$ and $65\%,$ respectively. For the
                      prediction of the 5-year progression-free survival,
                      Kaplan-Meier estimators based on the molecular subtype, a
                      Support Vector Machine based on methylation, and an
                      integrated model based on clinical factors, CNV data, and
                      predicted methylation scores achieved balanced accuracies of
                      $66\%,$ $68\%,$ and $73\%,$ respectively. Excluding samples
                      with low prediction scores resulted in balanced accuracies
                      of over $80\%.$ In sum, our large-scale analysis of
                      ependymomas provides robust information about molecular
                      features and their clinical meaning. Our data are
                      particularly relevant for rare and hardly explored tumor
                      subtypes and seemingly benign variants that display higher
                      recurrence rates than previously believed.},
      keywords     = {Humans / Ependymoma / Progression-Free Survival / Protein
                      Processing, Post-Translational / DNA methylation (Other) /
                      Ependymoma (Other) / Machine learning (Other) / Molecular
                      types (Other) / Survival (Other)},
      cin          = {FM01 / B360 / HD01 / B062},
      ddc          = {610},
      cid          = {I:(DE-He78)FM01-20160331 / I:(DE-He78)B360-20160331 /
                      I:(DE-He78)HD01-20160331 / I:(DE-He78)B062-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38265522},
      doi          = {10.1007/s00401-023-02674-x},
      url          = {https://inrepo02.dkfz.de/record/287282},
}