Genetic Study Identifies Mutations in Pediatric Cancers


In recent years, scientists have used genetic analysis of tumors to make landmark discoveries in identifying mutations that give rise to certain adult cancers, such as melanoma, lung cancer, and gastrointestinal stromal tumors. By comparison, very few such studies have been conducted in pediatric tumors.

Now, Memorial Sloan Kettering researchers have performed the first large-scale analysis of several pediatric cancers to identify mutations and potential targets for therapies. In two pediatric tumor types, investigators found mutations already known to cause some adult cancers.

“These mutations are clinically relevant and therefore good targets for therapies that block specific disease pathways,” says pediatric oncologist Neerav Shukla, who led the study. “This could open the door to targeted therapies for pediatric cancers, which have been lacking. Apart from that, these mutations could also help physicians decide the best approach with current treatments. In the future, we may want to start testing pediatric patients for some of these mutations at diagnosis.”

To perform the study, researchers used Memorial Sloan Kettering’s extensive bank of tumor samples and a powerful mutation detection technology called Sequenom. The team analyzed DNA from 380 samples of four pediatric cancers — neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, and desmoplastic small round cell tumors. Specifically, they looked to see whether mutations were present at 275 DNA sites where mutations had been frequently reported in other cancers — and therefore likely to be activating, or cancer promoting.

Neuroblastoma and the embryonal form of rhabdomyosarcoma, in particular, had a significant number of samples with mutations in genes that regulate growth signaling, a defect implicated in many adult cancers. The findings appear in the February 1 issue of Clinical Cancer Research.

The Sequenom technology is already routinely used at Memorial Sloan Kettering for genetic testing of several adult cancers. These tests were developed by molecular pathologist Marc Ladanyi, the study’s senior author, who adds, “With the system for studying tumors already in place, it would be simple to start using this approach in pediatric cancers.”