Neural crest development and neuroblastoma tumorigenesis

Neuroblastoma arises during the course of embryonal neural crest specification and differentiation. This process involves a programmed epithelial-to-mesenchymal transition (EMT) of multipotent early neural crest cells and generates a plethora of distinct tissues, including the sympathoadrenal lineages. Disruption of this normal developmental process with distinct oncogenic drivers (eg, MYCN of ALK oncogenes), at different times, can lead to multiple subtypes of neuroblastoma tumors. Interaction between different epigenetic and genetic drivers complicates the task of defining a primary oncogenic pathway for neuroblastoma. This results in a wide range of pathology, biology, and response to therapy.