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

Fredlund, Elina LU ; Andersson, Stina LU ; Hilgert, Elien ; Monferrer, Ezequiel ; Álvarez-Hernán, Guadalupe LU ; Karakaya, Sinan LU ; Loontiens, Siebe ; Bek, Jan Willem ; Gregor, Tomas LU and Lecomte, Estelle LU , et al. (2024) In Science Advances 10(25).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Science Advances
volume
10
issue
25
article number
eado1583
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • scopus:85196893870
  • pmid:38905335
ISSN
2375-2548
DOI
10.1126/sciadv.ado1583
language
English
LU publication?
yes
id
66a2a5ed-c7c3-4909-b7af-f4b678f2987a
date added to LUP
2024-07-23 17:49:07
date last changed
2024-07-24 03:00:03
@article{66a2a5ed-c7c3-4909-b7af-f4b678f2987a,
  abstract     = {{<p>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.</p>}},
  author       = {{Fredlund, Elina and Andersson, Stina and Hilgert, Elien and Monferrer, Ezequiel and Álvarez-Hernán, Guadalupe and Karakaya, Sinan and Loontiens, Siebe and Bek, Jan Willem and Gregor, Tomas and Lecomte, Estelle and Magnusson, Emma and Miltenyte, Enrika and Cabirol, Marie and Kyknas, Michail and Engström, Niklas and Henriksson, Marie Arsenian and Hammarlund, Emma and Rosenblum, Jared S. and Noguera, Rosa and Speleman, Frank and van Nes, Johan and Mohlin, Sofie}},
  issn         = {{2375-2548}},
  language     = {{eng}},
  number       = {{25}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science Advances}},
  title        = {{MOXD1 is a lineage-specific gene and a tumor suppressor in neuroblastoma}},
  url          = {{http://dx.doi.org/10.1126/sciadv.ado1583}},
  doi          = {{10.1126/sciadv.ado1583}},
  volume       = {{10}},
  year         = {{2024}},
}