Pediatric Cancer Research

Neuroblastoma

Solving the Mysteries

For decades, the causes of neuroblastoma have eluded researchers the world over.

That makes Children's Hospital's recent accomplishments all the more astonishing: in the space of just a few years, CHOP researchers have made several important discoveries that offer new insights into the genetic roots of this rare and complex childhood cancer.

One research team, led by John M. Maris, M.D., and Yael Mossé, M.D., identified mutations in the ALK gene as the main cause of the hereditary form of neuroblastoma The team also found that the same mutations can occur in the cancer cells in the nonhereditary form of the disease. This is the type of mutation that cancer cells can get "addicted" to, and drugs can be designed to target this addiction. Findings from this study were published in the prestigious journal Nature.

Other studies compared the genes of 5,000 children who have neuroblastoma to those of 10,000 healthy children, which led to the discovery of three genes that are involved in neuroblastoma and helped researchers identify why some children get the disease and others don't. Researchers hope that the results of these genome-wide association studies, which were published in Nature, Nature Genetics and the New England Journal of Medicine, will lead them to an even better understanding of how and why neuroblastoma develops.

The discovery of the ALK gene mutations has already led to a clinical trial of a promising new drug as well as a genetic test to identify patients at risk for neuroblastoma. Mosse says many more breakthroughs still lie ahead.

"The key next step for us is to try to really understand the role of ALK in neuroblastoma," she says. "We're just at the tip of the iceberg."

Source: Cause for Hope: CHOP Cancer Center Annual Report 2009