% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Wiestler:128540,
      author       = {B. P. O. Wiestler$^*$ and D. Capper$^*$ and V.
                      Hovestadt$^*$ and M. Sill$^*$ and D. Jones$^*$ and C.
                      Hartmann$^*$ and J. Felsberg$^*$ and M. Platten$^*$ and W.
                      Feiden and K. Keyvani and S. Pfister$^*$ and O. Wiestler$^*$
                      and R. Meyermann and G. Reifenberger$^*$ and T. Pietsch and
                      A. von Deimling$^*$ and M. Weller$^*$ and W. Wick$^*$},
      title        = {{A}ssessing {C}p{G} island methylator phenotype, 1p/19q
                      codeletion, and {MGMT} promoter methylation from
                      epigenome-wide data in the biomarker cohort of the {NOA}-04
                      trial.},
      journal      = {Neuro-Oncology},
      volume       = {16},
      number       = {12},
      issn         = {1523-5866},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2017-04556},
      pages        = {1630 - 1638},
      year         = {2014},
      abstract     = {Molecular biomarkers including isocitrate dehydrogenase 1
                      or 2 (IDH1/2) mutation, 1p/19q codeletion, and
                      O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter
                      methylation may improve prognostication and guide treatment
                      decisions for patients with World Health Organization (WHO)
                      anaplastic gliomas. At present, each marker is individually
                      tested by distinct assays. Illumina Infinium
                      HumanMethylation450 BeadChip arrays (HM450) enable the
                      determination of large-scale methylation profiles and
                      genome-wide DNA copy number changes. Algorithms have been
                      developed to detect the glioma CpG island methylator
                      phenotype (G-CIMP) associated with IDH1/2 mutation, 1p/19q
                      codeletion, and MGMT promoter methylation using a single
                      assay.Here, we retrospectively investigated the diagnostic
                      and prognostic performance of these algorithms in comparison
                      to individual marker testing and patient outcome in the
                      biomarker cohort (n = 115 patients) of the NOA-04
                      trial.Concordance for IDH and 1p/19q status was very high:
                      In $92\%$ of samples, the HM450 and reference data agreed.
                      In discordant samples, survival analysis by Kaplan-Meier and
                      Cox regression analyses suggested a more accurate assessment
                      of biological phenotype by the HM450 analysis. The
                      HM450-derived MGMT-STP27 model to calculate MGMT promoter
                      methylation probability revealed this aberration in a
                      significantly higher fraction of samples than conventional
                      methylation-specific PCR, with 87 of 91 G-CIMP tumors
                      predicted as MGMT promoter-methylated. Pyrosequencing of
                      discordant samples confirmed the HM450 assessment in 14 of
                      17 cases.G-CIMP and 1p/19q codeletion are reliably
                      detectable by HM450 analysis and are associated with
                      prognosis in the NOA-04 trial. For MGMT, HM450 suggests
                      promoter methylation in the vast majority of G-CIMP tumors,
                      which is supported by pyrosequencing.},
      keywords     = {Biomarkers (NLM Chemicals) / Tumor Suppressor Proteins (NLM
                      Chemicals) / Isocitrate Dehydrogenase (NLM Chemicals) / DNA
                      Modification Methylases (NLM Chemicals) / MGMT protein,
                      human (NLM Chemicals) / DNA Repair Enzymes (NLM Chemicals)},
      cin          = {G370 / G380 / B060 / C060 / B062 / G160 / L401 / M010 /
                      L101},
      ddc          = {610},
      cid          = {I:(DE-He78)G370-20160331 / I:(DE-He78)G380-20160331 /
                      I:(DE-He78)B060-20160331 / I:(DE-He78)C060-20160331 /
                      I:(DE-He78)B062-20160331 / I:(DE-He78)G160-20160331 /
                      I:(DE-He78)L401-20160331 / I:(DE-He78)M010-20160331 /
                      I:(DE-He78)L101-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:25028501},
      pmc          = {pmc:PMC4232086},
      doi          = {10.1093/neuonc/nou138},
      url          = {https://inrepo02.dkfz.de/record/128540},
}