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@ARTICLE{Aichmller:154204,
      author       = {C. Aichmüller$^*$ and M. Iskar$^*$ and D. T. W. Jones$^*$
                      and A. Korshunov$^*$ and B. Radlwimmer$^*$ and M. Kool$^*$
                      and A. Ernst$^*$ and S. M. Pfister$^*$ and P. Lichter$^*$
                      and M. Zapatka$^*$},
      title        = {{P}ilocytic {A}strocytoma demethylation and transcriptional
                      landscapes link b{ZIP} transcription factors to immune
                      response.},
      journal      = {Neuro-Oncology},
      volume       = {22},
      number       = {9},
      issn         = {1523-5866},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2020-00660},
      pages        = {1327-1338},
      year         = {2020},
      note         = {#EA:B060#LA:B060#2020 Sep 29;22(9):1327-1338},
      abstract     = {Pilocytic Astrocytoma (PA) is the most common pediatric
                      brain tumor. While genome and transcriptome landscapes are
                      well-studied, data of the complete methylome, tumor cell
                      composition and immune infiltration are scarce.We generated
                      whole genome bisulfite sequence data (WGBS) of nine PAs and
                      16 control samples and integrated available 154 PA and 57
                      control methylation array data. RNA sequence data of 49 PAs
                      and 11 control samples as well as gene expression arrays of
                      248 PAs and 28 controls were used to assess transcriptional
                      activity.DNA-methylation patterns of partially-methylated
                      domains (PMDs) suggested high stability of the methylomes
                      during tumorigenesis. Comparing tumor and control tissues of
                      infra- and supratentorial location using methylation arrays
                      revealed site specific pattern. Analysis of WGBS data
                      revealed 9381 significantly differentially methylated
                      regions (DMRs) in PA vs. control tissue. Enhancers and
                      transcription factor (TF) motifs of five distinct TF
                      families were found to be enriched in DMRs. Methylation
                      together with gene expression data based in-silico tissue
                      deconvolution analysis indicated a striking variation in the
                      immune cell infiltration in PA. A TF network analysis showed
                      a regulatory relation between bZIP transcription factors and
                      genes involved in immune related processes.We provide
                      evidence for a link of focal methylation differences and
                      differential gene expression to immune infiltration.},
      cin          = {B060 / B360 / HD01 / B062 / B300 / B420},
      ddc          = {610},
      cid          = {I:(DE-He78)B060-20160331 / I:(DE-He78)B360-20160331 /
                      I:(DE-He78)HD01-20160331 / I:(DE-He78)B062-20160331 /
                      I:(DE-He78)B300-20160331 / I:(DE-He78)B420-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32052037},
      doi          = {10.1093/neuonc/noaa035},
      url          = {https://inrepo02.dkfz.de/record/154204},
}