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@ARTICLE{Hovestadt:120695,
      author       = {V. Hovestadt$^*$ and D. Jones$^*$ and S. Picelli$^*$ and W.
                      Wang$^*$ and M. Kool$^*$ and P. A. Northcott$^*$ and M.
                      Sultan and K. Stachurski and M. Ryzhova and H.-J. Warnatz
                      and M. Ralser and S. Brun and J. Bunt and N. Jäger$^*$ and
                      K. Kleinheinz$^*$ and S. Erkek$^*$ and U. Weber$^*$ and C.
                      C. Bartholomae$^*$ and C. von Kalle$^*$ and C. Lawerenz$^*$
                      and J. Eils$^*$ and J. Koster and R. Versteeg and T.
                      Milde$^*$ and O. Witt$^*$ and S. Schmidt$^*$ and S. Wolf$^*$
                      and T. Pietsch and S. Rutkowski and W. Scheurlen and M. D.
                      Taylor and B. Brors$^*$ and J. Felsberg$^*$ and G.
                      Reifenberger$^*$ and A. Borkhardt$^*$ and H. Lehrach and R.
                      J. Wechsler-Reya and R. Eils$^*$ and M.-L. Yaspo and P.
                      Landgraf and A. Korshunov$^*$ and M. Zapatka$^*$ and B.
                      Radlwimmer$^*$ and S. Pfister$^*$ and P. Lichter$^*$},
      title        = {{D}ecoding the regulatory landscape of medulloblastoma
                      using {DNA} methylation sequencing.},
      journal      = {Nature},
      volume       = {510},
      number       = {7506},
      issn         = {1476-4687},
      address      = {London [u.a.]},
      publisher    = {Nature Publ. Group},
      reportid     = {DKFZ-2017-01121},
      pages        = {537 - 541},
      year         = {2014},
      abstract     = {Epigenetic alterations, that is, disruption of DNA
                      methylation and chromatin architecture, are now acknowledged
                      as a universal feature of tumorigenesis. Medulloblastoma, a
                      clinically challenging, malignant childhood brain tumour, is
                      no exception. Despite much progress from recent genomics
                      studies, with recurrent changes identified in each of the
                      four distinct tumour subgroups (WNT-pathway-activated,
                      SHH-pathway-activated, and the less-well-characterized Group
                      3 and Group 4), many cases still lack an obvious genetic
                      driver. Here we present whole-genome bisulphite-sequencing
                      data from thirty-four human and five murine tumours plus
                      eight human and three murine normal controls, augmented with
                      matched whole-genome, RNA and chromatin immunoprecipitation
                      sequencing data. This comprehensive data set allowed us to
                      decipher several features underlying the interplay between
                      the genome, epigenome and transcriptome, and its effects on
                      medulloblastoma pathophysiology. Most notable were highly
                      prevalent regions of hypomethylation correlating with
                      increased gene expression, extending tens of kilobases
                      downstream of transcription start sites. Focal regions of
                      low methylation linked to transcription-factor-binding sites
                      shed light on differential transcriptional networks between
                      subgroups, whereas increased methylation due to
                      re-normalization of repressed chromatin in DNA methylation
                      valleys was positively correlated with gene expression.
                      Large, partially methylated domains affecting up to
                      one-third of the genome showed increased mutation rates and
                      gene silencing in a subgroup-specific fashion. Epigenetic
                      alterations also affected novel medulloblastoma candidate
                      genes (for example, LIN28B), resulting in alternative
                      promoter usage and/or differential messenger RNA/microRNA
                      expression. Analysis of mouse medulloblastoma and
                      precursor-cell methylation demonstrated a somatic origin for
                      many alterations. Our data provide insights into the
                      epigenetic regulation of transcription and genome
                      organization in medulloblastoma pathogenesis, which are
                      probably also of importance in a wider developmental and
                      disease context.},
      keywords     = {Chromatin (NLM Chemicals) / Histones (NLM Chemicals) /
                      LIN28B protein, human (NLM Chemicals) / RNA-Binding Proteins
                      (NLM Chemicals) / Transcription Factors (NLM Chemicals)},
      cin          = {B060 / B062 / B080 / G100 / G340 / W190 / L401 / L101 /
                      G200},
      ddc          = {070},
      cid          = {I:(DE-He78)B060-20160331 / I:(DE-He78)B062-20160331 /
                      I:(DE-He78)B080-20160331 / I:(DE-He78)G100-20160331 /
                      I:(DE-He78)G340-20160331 / I:(DE-He78)W190-20160331 /
                      I:(DE-He78)L401-20160331 / I:(DE-He78)L101-20160331 /
                      I:(DE-He78)G200-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:24847876},
      doi          = {10.1038/nature13268},
      url          = {https://inrepo02.dkfz.de/record/120695},
}