Developmental Programs in Neuroblastoma

Neuroblastoma is an embryonal tumor, which originates from the developing sympathetic nervous system (Hoehner et al. Lab Investig 75:659–75, 1996). Primary tumors frequently arise from the adrenal gland or pre- and paravertebral sympathetic ganglia in thorax, abdomen, neck, or pelvis (Maris et al. Lancet. 369:2106–20, 2007). Therefore, it has been suggested that the tumors develop from common progenitors of sympathetic neurons and adrenal chromaffin cells. However, the definitive cell of origin remains unknown (Ratner et al. Ann Neurol. 80:13–23, 2016). The current knowledge about the development of the sympathetic nervous system, including sympathetic neurons and adrenal chromaffin cells, is incomplete and primarily based on experiments in mice and chicken. In contrast, human development has been largely unexplored due to the relative inaccessibility of developing human tissue and the lack of suitable methods to study human development. More recently, developing adrenal glands, sympathetic ganglia, and neural crest tissue covering various developmental stages, were studied by single-nucleus/cell RNA sequencing (snRNA-seq/scRNA-seq) to shed light on the normal development of sympathoadrenal cells in humans (Dong et al. Cancer Cell. 38:716–33. e716, 2020; Jansky et al. Nat Genet. 53:683–93, 2021; Kameneva et al. Nat Genet. 2021;53:694–706; Kildisiute et al. Sci Adv. 2021;7:eabd3311). In addition, neuroblastomas were studied by snRNA-seq/scRNA-seq and transcriptomes were compared to those of developing normal sympathoadrenal cells to gain insights into the developmental origins of neuroblastoma (Dong et al. Cancer Cell. 38:716–33. e716, 2020; Jansky et al. Nat Genet. 53:683–93, 2021; Kameneva et al. Nat Genet. 2021;53:694–706; Kildisiute et al. Sci Adv. 2021;7:eabd3311). This chapter summarizes these latest studies and provides novel insights into the activity of developmental programs in neuroblastoma.