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Updated: Jun 23, 2025
Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
Published on: August 25, 2021
MOXD1 is a lineage-specific gene and a tumor suppressor in neuroblastoma
Elina Fredlund1,2,3, Stina Andersson1,2,3, Elien Hilgert4
1Division of Pediatrics, Department of Clinical Sciences, Lund University, Lund, Sweden.
Abstract:
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.
Insights
Loss of the MOXD1 gene in neuroblastoma is linked to advanced disease. This study reveals MOXD1 as a crucial tumor suppressor in this childhood cancer, offering new therapeutic avenues.
Area of Science:
- Developmental biology
- Pediatric oncology
- Cancer genetics
Background:
- Neuroblastoma, a childhood cancer, has poorly understood embryonic origins.
- Limited models hinder studies of early tumor-driving events.
Purpose of the Study:
- To investigate the role of the gene MOXD1 in neuroblastoma development.
- To identify potential therapeutic targets for neuroblastoma.
Main Methods:
- Analysis of RNA sequencing data from human neuroblastoma samples.
- Single-cell RNA sequencing of neuroblastoma cells and fetal adrenal glands.
- In vivo modeling using zebrafish, chick, and mouse.
Main Results:
- Loss of MOXD1 expression correlates with advanced neuroblastoma and poorer outcomes.
- MOXD1 acts as a determinant of tumor development across multiple models.
- MOXD1 expression is conserved and restricted to specific cell types in normal development.
Conclusions:
- MOXD1 is identified as a lineage-restricted tumor suppressor gene in neuroblastoma.
- Findings support further stratification of neuroblastoma tumors.
- This research opens avenues for novel therapeutic interventions.
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