Abstract
Many pediatric brain tumors (pBTs) may result from the interplay of environmental factors with biological mechanisms at critical developmental periods in a child’s life. While several genetic disorders have been linked to development of pBTs, many pBTs may result from low-penetrant gene alterations in common pathways. Importantly, alterations and pathways that may be important to etiology in certain tumor types may not play a role in other pBT types. It is probable that heterogeneity in alterations, and possibly even pathways, exists within tumor groups as well. Identification of which pathways are most significant in the etiology of each pBT type will be critical in developing therapies for these tumors. While therapies for single gene mutations have been successful in the past for certain cancers, it is possible that therapies based on pathway inhibition will prove to be more successful in the treatment of tumors that have several mutations throughout a pathway such as pBTs. This chapter describes the current state of the research on environmental, genetic, and epigenetic factors possibly involved in the development of pBTs. It covers epidemiological research on environmental factors that have been investigated in relation to pBTs, the involvement of neural stem cells, progenitor cells, and developmental pathways in the etiology of pBTs, the genetic and epigenetic alterations that have been identified in common pBTs, and how these factors may interact with mitochondrial-nuclear signaling to increase individual susceptibility to pBTs.