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@ARTICLE{Mock:130182,
      author       = {A. Mock and C. Geisenberger and C. Orlik and R. Warta and
                      C. Schwager$^*$ and C. Jungk and C. Dutruel and L.
                      Geiselhart and D. Weichenhan$^*$ and M. Zucknick$^*$ and
                      A.-K. Nied and S. Friauf and J. Exner and D. Capper$^*$ and
                      C. Hartmann and B. Lahrmann and N. Grabe and J. Debus$^*$
                      and A. von Deimling$^*$ and O. Popanda$^*$ and C. Plass$^*$
                      and A. Unterberg and A. Abdollahi$^*$ and P. Schmezer$^*$
                      and C. Herold-Mende},
      title        = {{LOC}283731 promoter hypermethylation prognosticates
                      survival after radiochemotherapy in {IDH}1 wild-type
                      glioblastoma patients.},
      journal      = {International journal of cancer},
      volume       = {139},
      number       = {2},
      issn         = {0020-7136},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2017-05262},
      pages        = {424 - 432},
      year         = {2016},
      abstract     = {MGMT promoter methylation status is currently the only
                      established molecular prognosticator in IDH wild-type
                      glioblastoma multiforme (GBM). Therefore, we aimed to
                      discover novel therapy-associated epigenetic biomarkers.
                      After enrichment for hypermethylated fractions using
                      methyl-CpG-immunoprecipitation (MCIp), we performed global
                      DNA methylation profiling for 14 long-term (LTS; >36 months)
                      and 15 short-term (STS; 6-10 months) surviving GBM patients.
                      Even after exclusion of the G-CIMP phenotype, we observed
                      marked differences between the LTS and STS methylome. A
                      total of 1,247 probes in 706 genes were hypermethylated in
                      LTS and 463 probes in 305 genes were found to be
                      hypermethylated in STS patients (p values < 0.05, log2
                      fold change ± 0.5). We identified 13 differentially
                      methylated regions (DMRs) with a minimum of four
                      differentially methylated probes per gene. Indeed, we were
                      able to validate a subset of these DMRs through a second,
                      independent method (MassARRAY) in our LTS/STS training set
                      (ADCY1, GPC3, LOC283731/ISLR2). These DMRs were further
                      assessed for their prognostic capability in an independent
                      validation cohort (n = 62) of non-G-CIMP GBMs from the
                      TCGA. Hypermethylation of multiple CpGs mapping to the
                      promoter region of LOC283731 correlated with improved
                      patient outcome (p = 0.03). The prognostic performance
                      of LOC283731 promoter hypermethylation was confirmed in a
                      third independent study cohort (n = 89), and was
                      independent of gender, performance (KPS) and MGMT status
                      (p = 0.0485, HR = 0.63). Intriguingly, the
                      prediction was most pronounced in younger GBM patients (<60
                      years). In conclusion, we provide compelling evidence that
                      promoter methylation status of this novel gene is a
                      prognostic biomarker in IDH1 wild-type/non-G-CIMP GBMs.},
      keywords     = {Isocitrate Dehydrogenase (NLM Chemicals) / IDH1 protein,
                      human (NLM Chemicals)},
      cin          = {E210 / C060 / C010 / G380 / E050 / L101},
      ddc          = {610},
      cid          = {I:(DE-He78)E210-20160331 / I:(DE-He78)C060-20160331 /
                      I:(DE-He78)C010-20160331 / I:(DE-He78)G380-20160331 /
                      I:(DE-He78)E050-20160331 / I:(DE-He78)L101-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:26934681},
      doi          = {10.1002/ijc.30069},
      url          = {https://inrepo02.dkfz.de/record/130182},
}