Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

New Insights into Neuroblastoma Tumor Suppressor may Provide Clues for Improved Treatment

Published: Thursday, August 15, 2013
Last Updated: Thursday, August 15, 2013
Bookmark and Share
Loss of a gene required for stem cells in the brain to turn into neurons may underlie the most severe forms of neuroblastoma, a deadly childhood cancer of the nervous system.

Published in Developmental Cell today, the findings also provide clues about how to improve treatment of this often-incurable tumor.

Neuroblastoma can appear in nervous tissue in the abdomen, chest and spine, among other regions of the body, and can spawn body-wracking metastasis. The most severe tumors respond poorly to treatment and the disease accounts for 15 percent of cancer deaths in children.

Johan Holmberg, PhD, at the Ludwig Institute for Cancer Research Stockholm took a close look at the role of the CHD5 tumor suppressor during normal nervous system development. Previous studies had shown that the gene CHD5 is often inactivated in the most severe forms of neuroblastoma, but little was known about its function in healthy tissue or how it operates. The study, which was conducted in close collaboration with colleagues at Trinity College, Dublin, Ireland, addressed these two key issues.

The researchers found that CHD5 is required for the cellular transition from a stem cell to a mature neuron. In one experiment, the researchers knocked down the CHD5 gene by injecting a small RNA into the brains of fetal mice while in the womb.

"The result was a complete absence of neurons," says Ludwig researcher Holmberg who is based at the Karolinska Institutet. “Instead of becoming neurons, the cells with CHD5 knocked down stayed in a limbo-like state between an actively-dividing stem cell and a mature nerve cell. It was a very robust effect," added Holmberg.

The researchers also dissected how CHD5 operates, showing that it sticks to certain modifications of histone proteins. These modifications help control how genes are turned on and off. In the absence of CHD5, key stem cell genes are not turned off, and genes required for neuronal maturation are not turned on. The findings highlight how the failure of a cell to properly mature into its terminal state can underlie cancer, a relatively understudied area of research.

"It is necessary for cells in the healthy nervous tissue to be able to go from stem cells to neurons," explains Holmberg. "If you lose this capacity, these cells become locked in an immature state, which might yield quite dangerous tumor cells, especially in combination with additional cancer-promoting cellular events.”

The research could also lead to new ways to treat neuroblastoma, perhaps using currently approved drugs. One component of neuroblastoma treatment is retinoic acid, a drug that can drive neuronal maturation. Holmberg and his colleagues found that knocking down the expression of CHD5 in more benign neuroblastoma cells blocked their capacity to mature in response to retinoic acid treatment. "These cells were completely insensitive to treatment, no matter how much we gave them, mirroring the same unresponsiveness to retinoic acid in the more malignant CHD5-negative neuroblastoma cells,” says Holmberg.

The results of these cell-based experiments are consistent with clinical findings that retinoic acid is often unsuccessful in patients with severe forms of the disease. Holmberg reasons that if CHD5 could be re-activated in such hard-to-treat patients, it might increase responsiveness to retinoic acid. The findings may also have relevance for other types of tumors. For instance, CHD5 is often inactivated in glioblastoma multiforme, the most common and most aggressive form of brain cancer in adults.

Funding for this research came in part from Science Foundation Ireland; the Health Research Board; the Swedish Cancer Society, the Swedish Research Council, the Lilian Sagen and Curt Eriksson Research Foundation; DBRM; the Swedish Childhood Cancer Foundation; the Danish National Research Foundation; the Lundbeck Foundation; and the Novo Nordisk Foundation.

Holmberg is the head of the head of the CNS Tumors and Development lab at the Ludwig Institute for Cancer Research Stockholm where he is based at the Karolinska Institutet.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,900+ scientific posters on ePosters
  • More than 5,300+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.


Scientific News
Big Genetics in BC: The American Society for Human Genetics 2016 Meeting
Themes at this year's meeting ranged from the verification, validation, and sharing of data, to the translation of laboratory findings into actionable clinical results.
Cancer Genetics: Key to Diagnosis, Therapy
When applied judiciously, cancer genetics directs caregivers to the right drug at the right time, while sparing patients of unnecessary or harmful treatments.
Accelerating the Detection of Foodborne Bacterial Outbreaks
The speed of diagnosis of foodborne bacterial outbreaks could be improved by a new technique developed by researchers at the Georgia Institute of Technology.
Top 10 Life Science Innovations of 2016
2016 has seen the release of some truly innovative products. To help you digest these developments, The Scientist have listed their top picks for the year.
Scientists Identify Unique Genomic Features in Testicular Cancer
The findings may shed light on factors in other cancers that influence their sensitivity to chemotherapy.
Secret Phenotypes: Disease Devils in Invisible Details
Algorithmic deep phenotyping exposes masses of hidden traits and possible subtle genetic connections relevant to unseen influences on disease.
Cracking the Code of a Deadly Virus
Researchers have exploited weaknesses in VEEV's genetic code, creating a far less deadly variant.
Hunting the Missing Link Between Genetics and the Environment
The International Phenome Centre Network (IPCN) works to transform healthcare through phenomics - the dynamic interactions between our genes and our environment.
Repurposing Genes for Brain Development
Mammalian bone gene may be repurposed to promote cognition in humans.
Enhancing CRISPR to Explore Further
Researchers have developed sOPTiKO, a more efficient and controllable CRISPR genome editing platform.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,900+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,300+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!