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@ARTICLE{Pfaff:134863,
      author       = {E. Pfaff$^*$ and T. Kessler$^*$ and G. P.
                      Balasubramanian$^*$ and A. Berberich$^*$ and D. Schrimpf$^*$
                      and A. Wick$^*$ and J. Debus$^*$ and A. Unterberg and M.
                      Bendszus and C. Herold-Mende and D. Capper and I.
                      Schenkel$^*$ and A. Eisenmenger$^*$ and S. Dettmer$^*$ and
                      B. Brors$^*$ and M. Platten$^*$ and S. Pfister$^*$ and A.
                      von Deimling$^*$ and D. Jones$^*$ and W. Wick$^*$ and F.
                      Sahm$^*$},
      title        = {{F}easibility of real-time molecular profiling for patients
                      with newly diagnosed glioblastoma without {MGMT} promoter
                      hypermethylation-the {NCT} {N}euro {M}aster {M}atch
                      ({N}2{M}2) pilot study.},
      journal      = {Neuro-Oncology},
      volume       = {20},
      number       = {6},
      issn         = {1523-5866},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2018-00653},
      pages        = {826 - 837},
      year         = {2018},
      note         = {Pfaff E*, Kessler T* (*first author") / David T. W. Jones,#
                      Wolfgang Wick,# and Felix Sahm# last authors},
      abstract     = {O6-methylguanine-DNA methyltransferase (MGMT) promoter
                      methylation status is a predictive biomarker in glioblastoma
                      patients. Glioblastoma without hypermethylated MGMT promoter
                      is largely resistant to treatment with temozolomide. These
                      patients are in particular need of new treatment approaches,
                      which are offered by biomarker-driven clinical trials with
                      targeted drugs based on molecular characterization of
                      individual tumors.In preparation for an upcoming clinical
                      study, a comprehensive molecular profiling approach was
                      undertaken on tissues from 43 glioblastoma patients
                      harboring an unmethylated MGMT promoter at diagnosis. The
                      diagnostic pipeline covered various levels of molecular
                      characteristics, including whole-exome sequencing,
                      low-coverage whole-genome sequencing, RNA sequencing, as
                      well as microarray-based gene expression profiling and DNA
                      methylation arrays.Complex multilayer molecular diagnostics
                      were feasible in this setting with a median turnaround time
                      of 4-5 weeks from surgery to the molecular tumor board. In
                      $35\%$ of cases, potentially relevant therapeutic decisions
                      were derived from the data. Alterations were most frequently
                      found in receptor tyrosine kinases, members of the
                      phosphoinositide 3-kinase/Akt/mechanistic target of
                      rapamycin and mitogen-activated protein kinase pathway as
                      well as cell cycle control and p53 regulation cascades.
                      Individual tumors harbored clonal alterations such as
                      oncogenic fusions of tyrosine kinases which constitute
                      promising targets for targeted therapies. A prioritization
                      algorithm is proposed to allocate patients with multiple
                      targets to the potentially best treatment option.With this
                      feasibility study, a comprehensive molecular profiling
                      approach for patients with newly diagnosed glioblastoma
                      harboring an unmethylated MGMT promoter is presented.
                      Analyses in this pilot cohort serve as a basis for trials
                      based on targetable alterations and on the question of
                      allocation of patients to the best treatment arm.},
      cin          = {B062 / L101 / G370 / G200 / G380 / E050 / G040 / G160},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)L101-20160331 /
                      I:(DE-He78)G370-20160331 / I:(DE-He78)G200-20160331 /
                      I:(DE-He78)G380-20160331 / I:(DE-He78)E050-20160331 /
                      I:(DE-He78)G040-20160331 / I:(DE-He78)G160-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29165638},
      pmc          = {pmc:PMC5961072},
      doi          = {10.1093/neuonc/nox216},
      url          = {https://inrepo02.dkfz.de/record/134863},
}