Origin and initiation mechanisms of neuroblastoma

• Published in: Cell and tissue research Vol. 372; no. 2; pp. 211 - 221
• Main Authors: Tsubota, Shoma, Kadomatsu, Kenji
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-05-2018; Springer; Springer Nature B.V
• Subjects: Adrenal glands; Adrenal medulla; Adrenal Medulla - pathology; Analysis; Animal models; Animals; Biomedical and Life Sciences; Biomedicine; Carcinogenesis - pathology; Children; Chromaffin cells; Chromaffin Cells - pathology; Disease Models, Animal; Epigenesis, Genetic; Epigenetic inheritance; Gene expression; Genetic engineering; Genetically modified animals; Genomes; Human Genetics; Humans; Malignancy; Molecular Medicine; Myc protein; Neural crest; Neural stem cells; Neuroblastoma; Neuroblastoma - genetics; Neuroblastoma - pathology; Pediatrics; Polycomb group proteins; Proteomics; Review; Reviews; Sympathetic ganglia; Sympathetic nervous system; Schwann cell precursors; MYCN; Neuroblastoma; Neural crest cells; Sympathoadrenal progenitors
• ISSN: 0302-766X; 1432-0878
• DOI: 10.1007/s00441-018-2796-z

Neuroblastoma is an embryonal malignancy that affects normal development of the adrenal medulla and paravertebral sympathetic ganglia in early childhood. Extensive studies have revealed the molecular characteristics of human neuroblastomas, including abnormalities at genome, epigenome and transcriptome levels. However, neuroblastoma initiation mechanisms and even its origin are long-standing mysteries. In this review article, we summarize the current knowledge about normal development of putative neuroblastoma sources, namely sympathoadrenal lineage of neural crest cells and Schwann cell precursors that were recently identified as the source of adrenal chromaffin cells. A plausible origin of enigmatic stage 4S neuroblastoma is also discussed. With regard to the initiation mechanisms, we review genetic abnormalities in neuroblastomas and their possible association to initiation mechanisms. We also summarize evidences of neuroblastoma initiation observed in genetically engineered animal models, in which epigenetic alterations were involved, including transcriptomic upregulation by N-Myc and downregulation by polycomb repressive complex 2. Finally, several in vitro experimental methods are proposed that hopefully will accelerate our comprehension of neuroblastoma initiation. Thus, this review summarizes the state-of-the-art knowledge about the mechanisms of neuroblastoma initiation, which is critical for developing new strategies to cure children with neuroblastoma.