Cerebellar development and medulloblastoma:origins and the role of the epigenome

Every year, in the Netherlands, more than hundred children are diagnosed with brain cancer, of which approximately 20 children are diagnosed with medulloblastoma. While medulloblastoma can also occur in adults, it is primarily a disease affecting children. Medulloblastoma is the most common malignant brain tumor in children and is located in the posterior region of the brain, known as the cerebellum or the little brain. Although 70% of the children survive, they often experience long-term consequences with various neurological problems due to the low specificity of current treatment strategies, such as chemotherapy, radiotherapy, and/or surgical resection.Medulloblastoma is a very heterogenous disease originating from different developmental time points, with different biology, using distinct signaling pathways and mechanisms and with diverse clinical outcomes.This heterogeneity presents an even greater challenge in treating medulloblastoma, as each therapy must be tailored to the specific characteristics of each patient's tumor type.The aim of the work presented in this thesis is to investigate and gain more insight into the complex interplay between different molecular players in the developing cerebellum and how their dysregulation can lead to the development of medulloblastoma. Additionally, we have attempted to further understand the striking differences between medulloblastoma in infants, children, and adults and to identify new age-specific targets