Neuroblastoma: When differentiation goes awry

Neuroblastoma is a leading cause of cancer-related death in children. Accumulated data suggest that differ-entiation arrest of the neural-crest-derived sympathoadrenal lineage contributes to neuroblastoma forma-tion. The developmental arrest of these cell types explains many biological features of the disease, including its cellular heterogeneity, mutational spectrum, spontaneous regression, and response to drugs that induce tumor cell differentiation. In this review, we provide evidence that supports the notion that arrested neural -crest-derived progenitor cells give rise to neuroblastoma and discuss how this concept could be exploited for clinical management of the disease.