Singapore, Aug 26, 2008: Scientists have discovered gene mutations that are the main cause of the inherited version of the childhood cancer neuroblastoma. In addition, the researchers found that the same mutations play a significant role in high-risk forms of non-inherited neuroblastoma, the more common form of the disease.

 

"This discovery enables us to offer the first genetic tests to families affected by the inherited form of this disease. Furthermore, because there already are drugs in development that target the same gene in adult cancers, we can soon begin testing those drugs in children with neuroblastoma," said Dr Yael P Mosse, pediatric oncologist, The Children's Hospital of Philadelphia, the first author of the study, published online in the journal Nature.

 

Neuroblastoma is the most common solid cancer of early childhood. It accounts for seven percent of all childhood cancers, but due to its often-aggressive nature, causes 15 percent of all childhood cancer deaths. It arises in the developing nerves of a child, often appearing as a tumor in the chest or abdomen.

 

Because only about 600 new cases of all forms of neuroblastoma occur annually in the US, familial (inherited) neuroblastoma is a very rare subset of a relatively uncommon disease. Scientists at Children's Hospital have studied familial neuroblastoma for the past 15 years, and the current study drew on family data collected from throughout the world.

 

Dr John M Maris, senior author of the current study and director of the Center for Childhood Cancer Research at Children's Hospital, leads a laboratory with the world's largest collection of neuroblastoma tissue samples, gathered through the multicenter Children's Oncology Group in the US and through multiple international collaborations.

 

Dr Maris said, "This is a very important discovery, as it not only helps us understand the genetic roots of this terrible disease, but also has led to dramatically new ideas for curative therapy."

 

The study team used high-speed, automated analytic equipment at the Center for Applied Genomics at Children's Hospital. By employing genome-wide scans to analyze DNA from the 10 most informative families with a history of neuroblastoma, Dr Mosse and her colleagues first discovered that a region of chromosome 2 was associated with the disease. Further sequencing of that region identified mutations in the anaplastic lymphoma kinase (ALK) gene in eight families with familial neuroblastoma.