Abstract
Dysregulated expression of the transcription factor MYCN is frequently detected in nervous system tumors such as childhood neuroblastoma. Here, gene amplification of MYCN is a single oncogenic driver inducing neoplastic transformation in neural crest-derived cells. This abnormal MYCN expression is one of the strongest predictors of poor prognosis. It is present at diagnosis and is never acquired during later tumorigenesis of MYCN non-amplified neuroblastoma. This suggests that increased MYCN expression is an early event in these cancers leading to a peculiar dysregulation of cells that results in embryonal or cancer stem-like qualities, such as increased self-renewal, apoptotic resistance, and metabolic flexibility.