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@ARTICLE{Sandn:120628,
      author       = {E. Sandén and C. Dyberg and C. Krona and G. Gallo-Oller
                      and T. K. Olsen and J. Enríquez Pérez and M. Wickström
                      and A. Estekizadeh and M. Kool$^*$ and E. Visse and T. J.
                      Ekström and P. Siesjö and J. I. Johnsen and A. Darabi},
      title        = {{E}stablishment and characterization of an orthotopic
                      patient-derived {G}roup 3 medulloblastoma model for
                      preclinical drug evaluation.},
      journal      = {Scientific reports},
      volume       = {7},
      issn         = {2045-2322},
      address      = {London},
      publisher    = {Nature Publishing Group},
      reportid     = {DKFZ-2017-01056},
      pages        = {46366 -},
      year         = {2017},
      abstract     = {Medulloblastomas comprise a heterogeneous group of tumours
                      and can be subdivided into four molecular subgroups (WNT,
                      SHH, Group 3 and Group 4) with distinct prognosis,
                      biological behaviour and implications for targeted
                      therapies. Few experimental models exist of the aggressive
                      and poorly characterized Group 3 tumours. In order to
                      establish a reproducible transplantable Group 3
                      medulloblastoma model for preclinical therapeutic studies,
                      we acquired a patient-derived tumour sphere culture and
                      inoculated low-passage spheres into the cerebellums of
                      NOD-scid mice. Mice developed symptoms of brain tumours with
                      a latency of 17-18 weeks. Neurosphere cultures were
                      re-established and serially transplanted for 3 generations,
                      with a negative correlation between tumour latency and
                      numbers of injected cells. Xenografts replicated the
                      phenotype of the primary tumour, including high degree of
                      clustering in DNA methylation analysis, high proliferation,
                      expression of tumour markers, MYC amplification and elevated
                      MYC expression, and sensitivity to the MYC inhibitor JQ1.
                      Xenografts maintained maintained expression of
                      tumour-derived VEGFA and stromal-derived COX-2. VEGFA, COX-2
                      and c-Myc are highly expressed in Group 3 compared to other
                      medulloblastoma subgroups, suggesting that these molecules
                      are relevant therapeutic targets in Group 3
                      medulloblastoma.},
      cin          = {B062},
      ddc          = {000},
      cid          = {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:28417956},
      pmc          = {pmc:PMC5394470},
      doi          = {10.1038/srep46366},
      url          = {https://inrepo02.dkfz.de/record/120628},
}