MOXD1 is a lineage-specific gene and a tumor suppressor in neuroblastoma

Menée à l'aide de lignées cellulaires de neuroblatomes puis de plusieurs modèles animaux (poissons zèbres, poussins et souris), cette étude met en évidence le rôle de suppresseur de tumeur de la mono-oxygénase MOXD1 et démontre que cette dernière est un marqueur spécifique des cellules mésenchymateuses ou immatures

Résumé en anglais

Neuroblastoma is a childhood developmental cancer; however, its embryonic origins remain poorly understood. Moreover, in-depth studies of early tumor-driving events are limited because of the lack of appropriate models. Herein, we analyzed RNA sequencing data obtained from human neuroblastoma samples and found that loss of expression of trunk neural crest–enriched gene MOXD1 associates with advanced disease and worse outcome. Further, by using single-cell RNA sequencing data of human neuroblastoma cells and fetal adrenal glands and creating in vivo models of zebrafish, chick, and mouse, we show that MOXD1 is a determinate of tumor development. In addition, we found that MOXD1 expression is highly conserved and restricted to mesenchymal neuroblastoma cells and Schwann cell precursors during healthy development. Our findings identify MOXD1 as a lineage-restricted tumor-suppressor gene in neuroblastoma, potentiating further stratification of these tumors and development of novel therapeutic interventions. MOXD1 is a tumor-suppressor gene and a lineage-specific marker for immature and mesenchymal cells in neuroblastoma.