Discovery advances childhood cancer work

Scripps Translational Science team plays part in neuroblastoma study

Researchers at Scripps Translational Science Institute in La Jolla contributed to a major genetic breakthrough, identifying the gene responsible for an inherited childhood cancer. Neuroblastoma, a cancer of the nervous system, claims 200,000 lives in the United States each year. While relatively rare, it has a survival rate of less than 40 percent and accounts for 15 percent of all childhood cancer deaths.

Pinpointing its source provides critical information for diagnostic screening and, hopefully, finding successful treatments.

“This gives us a target; the process for drug development can start,” said Nicholas Schork, Ph.D., director of biostatistics at the Scripps institute.

Schork and Scripps scholar Ali Torkamani, Ph.D. were part of the global research effort led by the Children’s Hospital of Philadelphia.

Hospital researchers looked for mutations in 176 genomes of 20 affected families and found several mutations that appeared to be linked with the cancer. Researchers then turned to Scripps to narrow down the list.

Genes make proteins, which are the building blocks of the body. Any mutations in them can be harmful or harmless depending on which part of the protein they disturb.

Using computer modeling, Schork and Torkamani identified exactly where the proteins were deformed, and thus if there would be deleterious effects.

The process was not extremely difficult, but it wasn’t simple either, Schork said. The only unusual element was finding the mutations were in harmful locations.

“We find all sorts of mutations but they tend to be neutral, they don’t do anything,” Schork said.

Their findings were confirmed by lab tests back at the hospital, and published in an online “Nature” article titled “Identification of ALK as a major familial neuroblastoma predisposition gene.”

Schork said their contribution was just one of several important pieces of the research puzzle.

However, its significance goes beyond this particular discovery, he said.

Computer modeling reduced the number of expensive laboratory tests required, streamlining the research process and helping overcome potential cost-prohibitions. Testing a huge number of mutations in a laboratory would be “way too costly,” Schork said.

“It sets a precedent for trying strategies for other forms of cancers,” Schork said. “It’s a long road, but the success with this rare form of cancer provides a ray of hope, a strategy for other cancers.”