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@ARTICLE{SextonOates:136810,
      author       = {A. Sexton-Oates and A. Dodgshun and V. Hovestadt$^*$ and D.
                      Jones$^*$ and D. M. Ashley and M. Sullivan and D. MacGregor
                      and R. Saffery},
      title        = {{M}ethylation profiling of paediatric pilocytic astrocytoma
                      reveals variants specifically associated with tumour
                      location and predictive of recurrence.},
      journal      = {Molecular oncology},
      volume       = {12},
      number       = {8},
      issn         = {1574-7891},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2018-01248},
      pages        = {1219 - 1232},
      year         = {2018},
      abstract     = {Childhood pilocytic astrocytomas (PA) are low-grade tumours
                      with an excellent prognosis. However, a minority,
                      particularly those in surgically inaccessible locations,
                      have poorer long-term outcome. At present, it is unclear
                      whether anatomical location in isolation, or in combination
                      with underlying biological variation, determines clinical
                      behaviour. Here, we have tested the utility of DNA
                      methylation profiling to inform tumour biology and to
                      predict behaviour in paediatric PA. Genome-wide DNA
                      methylation profiles were generated for 117 paediatric PAs.
                      Using a combination of analyses, we identified DNA
                      methylation variants specific to tumour location and
                      predictive of behaviour. Receiver-operating characteristic
                      analysis was used to test the predictive utility of clinical
                      and/or DNA methylation features to classify tumour behaviour
                      at diagnosis. Unsupervised analysis distinguished three
                      methylation clusters associated with tumour location
                      (cortical, midline and infratentorial). Differential
                      methylation of 5404 sites identified enrichment of genes
                      involved in embryonic nervous system development. Specific
                      hypermethylation of NEUROG1 and NR2E1 was identified as a
                      feature of cortical tumours. A highly accurate method to
                      classify tumours according to behaviour, which combined
                      three clinical features (age, location and extent of
                      resection) and methylation level at a single site, was
                      identified. Our findings show location-specific epigenetic
                      profiles for PAs, potentially reflecting their cell type of
                      origin. This may account for differences in clinical
                      behaviour according to location independent of
                      histopathology. We also defined an accurate method to
                      predict tumour behaviour at diagnosis. This warrants further
                      testing in similar patient cohorts.},
      cin          = {B060 / B062},
      ddc          = {610},
      cid          = {I:(DE-He78)B060-20160331 / I:(DE-He78)B062-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:28388012},
      pmc          = {pmc:PMC6068350},
      doi          = {10.1002/1878-0261.12062},
      url          = {https://inrepo02.dkfz.de/record/136810},
}