Central nervous system (CNS) tumors represent the second most prevalent group of cancers
in children and adolescents, yet account for the majority of childhood cancer-related deaths and considerable
morbidity among survivors, due to high-intensity non-selective standard therapies delivered to
immature nervous system structures undergoing development. These tumors arise at different ages –not
infrequently very early in life-, in different locations and cellular contexts, have varied cell types of origin,
and have heterogeneous responses to the “classic” current therapeutic approaches. Demographic,
radiologic and morphological characterization have several limitations, putting into the “classic boxes”
heterogeneous tumors that are diverse in their genetic and epigenetic background and that will likely
behave biologically different. Given that, epigenetic disruption (i.e. DNA methylation, histone modification
and chromatin remodeling) is a common feature identified more and more frequently in pediatric
cancer, it is logical to speculate that interrogating epigenetic marks may help to further define the molecular
profile, and therefore tumor biology, evolution and treatment of these tumors. An integrated approach
that incorporates traditional features complemented with genetic and epigenenetic specific
markers offers tremendous promise to “risk-group” stratification and better prognostication. Also, it
will help unveil the key driver pathways for tumor formation and for the discovery of targeted therapy
for neoplasms that appear in the developing brain, facilitating early identification of therapy responders
and track accurately disease progression. In this paper, we reviewed the most representative pediatric
brain tumors where epigenetic alterations have been identified as initiating or driving events in tumor
development, maintenance or progression.
Splicing Dysregulation as Oncogenic Driver and Passenger Factor in Brain Tumors
