Epigenetic mechanisms regulating neural development and pediatric brain tumor formation

Pediatric brain tumors are the leading cause of cancer-related death in children, and among them, embryonal tumors represent the largest group with an associated poor prognosis and long-term morbidity for survivors. The field of cancer epigenetics has emerged recently as an important area of investigation and causation of a variety of neoplasms, and is defined as alterations in gene expression without changes in DNA sequence. The best studied epigenetic modifications are DNA methylation, histone modifications, and RNA-based mechanisms. These modifications play an important role in normal development and differentiation but their dysregulation can lead to altered gene function and cancer. In this review the authors describe the mechanisms of normal epigenetic regulation, how they interplay in neuroembryogenesis, and how these can cause brain tumors in children when dysregulated. The potential use of epigenetic markers to design more effective treatment strategies for children with malignant brain tumors is also discussed.