Genetic Study Identifies Mutations in Pediatric Cancers

Pictured: Marc Ladanyi & Laetitia Borsu

Molecular pathologist Marc Ladanyi (left) and genomics project manager Laetitia Borsu

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 – neuroblastoma and the embryonic form of rhabdomyosarcoma — investigators found mutations already known to cause some adult cancers.

These mutations are found only in the tumor cells, and not the normal cells of these patients. Therefore, these children with pediatric cancers are not at higher risk for developing adult cancers later.

“What the finding suggests is that these mutations are clinically relevant and therefore good targets for therapies that hinder specific disease pathways,” says pediatric oncologist Neerav Shukla, who led the study published on February 1 in the journal Clinical Cancer Research.

“This could open the door to targeted therapies for pediatric cancers, which have been lacking,” he adds. “Apart from that, these mutations can likely help physicians determine the best approach with current treatments. In the future, we may want to start testing pediatric patients for some of these mutations at diagnosis.”

Cutting-Edge Resources at Work

To perform one of the first-ever studies in pediatric tumors, researchers used Memorial Sloan Kettering’s extensive bank of tumor samples and a powerful mutation detection technology called Sequenom, which is already routinely used for genetic testing of several adult cancers.

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 had a significant number of samples with mutations in genes that regulate growth signaling, a defect implicated in many adult cancers.

Molecular pathologist Marc Ladanyi, the study’s senior author and developer of the genetic tests used at Memorial Sloan Kettering for adult cancers, adds, “With the system for studying tumors already in place, it would be simple to start using this approach in pediatric cancers.”


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