Researchers find gene location that gives rise to neuroblastoma, an aggressive childhood cancer

First finding of origin of a puzzling pediatric tumor

Using advanced gene-hunting technology, an international team of researchers has for the first time identified a chromosome region that is the source of genetic events that give rise to neuroblastoma, an often fatal childhood cancer.

The investigators found that the presence of common DNA variations in a region of chromosome 6 raises the risk that a child will develop a particularly aggressive form of neuroblastoma, a cancer of the peripheral nervous system that usually appears as a solid tumor in the chest or abdomen. Neuroblastoma accounts for 7 percent of all childhood cancers, but due to its aggressive nature, causes 15 percent of all childhood cancer deaths.

“Until now we had very few clues as to what causes neuroblastoma,” said pediatric oncologist John M. Maris, M.D., who led the study at The Children’s Hospital of Philadelphia, where he is the director of the Center for Childhood Cancer Research. “Although there is much work to be done,” added Maris, “understanding this cancer’s origin provides a starting point for developing novel treatments.” The study team reported its findings in today’s Online First version of the New England Journal of Medicine.

Neuroblastoma is the most common solid cancer of early childhood and has long been known to include subtypes that behave very differently. Some cases strike infants but spontaneously disappear with minimal treatment, while other cases in older children may be relentlessly aggressive from the start.

Researchers at Children’s Hospital and colleagues in the multicenter Children’s Oncology Group have for decades analyzed tumors for characteristics such as amplified levels of a cancer-causing gene and deletions of chromosome material. They used those tumor peculiarities to classify neuroblastoma into risk levels that guide oncologists toward the most appropriate treatments. “Properly defining risk level helps us to avoid the twin pitfalls of undertreating or overtreating any given child with neuroblastoma,” added Maris.