Expression of the CHD5 gene is frequently down-regulated in neuroblastomas, and patients whose tumors lacked CHD5 expression were more likely to have shorter event-free and overall survival compared with patients whose tumors expressed CHD5, according to a study in the June 24 issue of the Journal of the National Cancer Institute.
Neuroblastoma tumors often lack one copy of a region on the short arm of chromosome 1, called 1p36.31. Garrett Brodeur, M.D., of the Children's Hospital of Philadelphia and colleagues previously identified the smallest region spanned by the deletion in more than 1,200 patient tumors and found that 23 genes were located within the region.
In the current study, Brodeur and colleagues examined the expression pattern of CHD5 in neuroblastoma cell lines and the impact of replacing the missing copy of this gene in animal models. They also looked at the association between expression of each of the 23 genes from the region and clinical outcome in 99 patients.
Although the remaining copy of the CHD5 gene is rarely mutated in neuroblastomas, the authors found that the gene is epigenetically silenced in neuroblastoma cell lines with 1p deletion. Patients whose tumors showed high expression of CHD5 protein had approximately 7-fold longer event-free and overall survival than those patients whose tumor showed low CHD5 expression. Other genes in the region did not show a consistent association with neuroblastoma prognostic features and patient outcomes.
"These results demonstrate that CHD5 expression is strongly associated with outcome in neuroblastomas, CHD5 is the likely target of 1p deletions in these tumors, and it may have a direct role in the biology and behavior of neuroblastomas," the authors write.
- Fujita et al. CHD5, a Tumor Suppressor Gene Deleted From 1p36.31 in Neuroblastomas. JNCI Journal of the National Cancer Institute, 2008; DOI: 10.1093/jnci/djn176
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