MYC promotes aggressive growth and metastasis of a WNT-medulloblastoma mouse model

Medulloblastoma (MB), the most common malignant pediatric brain tumor, comprises four molecularly and clinically distinct subgroups (termed WNT, SHH, Group3, and Group4). Prognosis varies based on genetic and pathological features associated with each molecular subgroup. WNT-MB, considered low-risk, are rarely metastatic and contain activating mutations in CTNNB1; Group3-MB, commonly classified as high-risk, are frequently metastatic and can contain genomic alterations resulting in elevated MYC expression. Here we compare model systems of low-risk WNT-MB and high-risk Group3-MB to identify tumor and microenvironment interactions that could contribute to features associated with prognosis. Compared to Group3-MB, we find that WNT-MB are enriched in gene sets related to extracellular matrix (ECM) regulation and cellular adhesion. Exogenous expression of MycT58A in a murine WNT-MB model significantly accelerates growth and results in metastatic disease. In addition to decreased ECM regulation and cell adhesion pathways, we also identified immune system interactions among the top down-regulated signaling pathways following MycT58A expression. Taken together, our data provides evidence that increased Myc-signaling can promote the growth and metastasis in a murine model of WNT-MB.