Establishment and characterization of an orthotopic patient-derived Group 3 medulloblastoma model for preclinical drug evaluation

Emma Sandén, Cecilia Dyberg, Cecilia Krona, Gabriel Gallo-Oller, Thale Kristin Olsen, Julio Enríquez Pérez, Malin Wickström, Atosa Estekizadeh, Marcel Kool, Edward Visse, Tomas J. Ekström, Peter Siesjö, John Inge Johnsen, Anna Darabi

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


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.

Original languageEnglish
Article number46366
JournalScientific Reports
Publication statusPublished - 18 Apr 2017
Externally publishedYes


Dive into the research topics of 'Establishment and characterization of an orthotopic patient-derived Group 3 medulloblastoma model for preclinical drug evaluation'. Together they form a unique fingerprint.

Cite this