TY  - JOUR
AU  - Sandén, Emma
AU  - Dyberg, Cecilia
AU  - Krona, Cecilia
AU  - Gallo-Oller, Gabriel
AU  - Olsen, Thale Kristin
AU  - Enríquez Pérez, Julio
AU  - Wickström, Malin
AU  - Estekizadeh, Atosa
AU  - Kool, Marcel
AU  - Visse, Edward
AU  - Ekström, Tomas J
AU  - Siesjö, Peter
AU  - Johnsen, John Inge
AU  - Darabi, Anna
TI  - Establishment and characterization of an orthotopic patient-derived Group 3 medulloblastoma model for preclinical drug evaluation.
JO  - Scientific reports
VL  - 7
SN  - 2045-2322
CY  - London
PB  - Nature Publishing Group
M1  - DKFZ-2017-01056
SP  - 46366 -
PY  - 2017
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:28417956
C2  - pmc:PMC5394470
DO  - DOI:10.1038/srep46366
UR  - https://inrepo02.dkfz.de/record/120628
ER  -