August 12, 2013, New York, NY 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, according to a Ludwig Cancer Research study. Published in Developmental Cell today, the findings also provide clues about how to improve the 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 absenc
|Contact: Rachel Steinhardt|
Ludwig Institute for Cancer Research