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@ARTICLE{Eckhardt:284645,
      author       = {A. Eckhardt and R. Drexler and M. Schoof and N. Struve and
                      D. Capper and C. Jelgersma and J. Onken$^*$ and P.
                      Harter$^*$ and K. Weber$^*$ and I. Divé and K. Rothkamm and
                      K. Hoffer and L. Klumpp and K. Ganser and C. Petersen and F.
                      Ricklefs and M. Kriegs and U. Schüller},
      title        = {{M}ean global {DNA} methylation serves as independent
                      prognostic marker in {IDH} wild type glioblastoma.},
      journal      = {Neuro-Oncology},
      volume       = {26},
      number       = {3},
      issn         = {1522-8517},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2023-02048},
      pages        = {503-513},
      year         = {2024},
      note         = {2024 Mar 4;26(3):503-513},
      abstract     = {The IDH wild type glioblastoma (GBM) patients have a
                      devastating prognosis. Here, we analyzed the potential
                      prognostic value of global DNA methylation of the tumors.DNA
                      methylation of 492 primary samples and 31 relapsed samples,
                      each treated with combination therapy, and of 148 primary
                      samples treated with radiation alone were compared with
                      patient survival. We determined the mean methylation values
                      and estimated the immune cell infiltration from the
                      methylation data. Moreover, the mean global DNA methylation
                      of 23 GBM cell lines was profiled and correlated to their
                      cellular radiosensitivity as measured by colony formation
                      assay.High mean DNA methylation levels correlated with
                      improved survival, which was independent from known risk
                      factors (MGMT promoter methylation, age, extent of
                      resection; p=0.009) and methylation subgroups. Notably, this
                      correlation was also independent of immune cell infiltration
                      since higher number of immune cells indeed was associated
                      with significantly better OS but lower mean methylation.
                      Radiosensitive GBM cell lines had a significantly higher
                      mean methylation than resistant lines (p=0.007), and
                      improved OS of patients treated with radiotherapy alone was
                      also associated with higher DNA methylation (p=0.002).
                      Furthermore, specimens of relapsed GBM revealed a
                      significantly lower mean DNA methylation compared to the
                      matching primary tumor samples (p=0.041).Our results
                      indicate that mean global DNA methylation is independently
                      associated with outcome in glioblastoma. The data also
                      suggest that a higher DNA methylation is associated with
                      better radiotherapy response and less aggressive phenotype,
                      both of which presumably contribute to the observed
                      correlation with OS.},
      keywords     = {DNA methylation (Other) / glioblastoma (Other) / overall
                      survival (Other) / radiotherapy response (Other)},
      cin          = {BE01 / FM01},
      ddc          = {610},
      cid          = {I:(DE-He78)BE01-20160331 / I:(DE-He78)FM01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37818983},
      doi          = {10.1093/neuonc/noad197},
      url          = {https://inrepo02.dkfz.de/record/284645},
}