CHD5 gene suppression tied to poor outcome in neuroblastomas

July 7, 2008

NEW YORK (Reuters Health) - Low CHD5 expression is associated with poorer outcome in patients with neuroblastomas, researchers report in the July 2nd issue of the Journal of the National Cancer Institute.

"CHD5 is a tumor suppressor gene that is deleted in at least a third of all neuroblastomas, especially the higher-risk tumors," senior investigator Dr. Garrett M. Brodeur, of Children's Hospital of Philadelphia, told Reuters Health. The tumors also often lack one copy of a region on the short arm of chromosome 1, called 1p36.31.

"Identification and characterization of this gene as the probable target of 1p36 deletions," Dr. Brodeur added, "will provide substantial insight into what causes high-risk neuroblastomas to occur, and possibly how to treat them more effectively."

Dr. Brodeur and his colleagues examined the expression pattern of CHD5 in neuroblastoma cell lines. They also studied the impact of replacing the missing copy of this gene in athymic mice with xenograft tumors. Finally, they looked at the association between expression of each of the 23 genes from the region and clinical outcome in 99 patients.

The investigators note that "there was clear suppression of both clonogenicity and xenograft tumor growth of CHD5-transfected clones, but only in tumors with 1p deletion."

Moreover, continued Dr. Brodeur, "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 demonstrate a consistent association with such events.

These studies, he continued, therefore "showed that assessment of CHD5 expression in tumors is a powerful predictor of outcome, even after correcting for other prognostic variables that are in current use."

"If validated," Dr. Brodeur said, "assessment of CHD5 expression could become a valuable prognostic marker to help predict outcome and select the most appropriate intensity of therapy."