Precision Therapy for Pediatric Cancers

Cancer is a genetic disease caused by driver mutations of germline and somatic DNA. With the rapid advances in next-generation sequencing (NGS) technologies, it is now possible to determine the exact DNA makeup of a tumor’s genome and the resultant RNA expression at base-pair resolution. The increasing robustness of NGS combined with advances in the capacity of computation is enabling genomics to be rapidly translated into the clinic. Through projects funded by the National Cancer Institute, such as The Cancer Genome Atlas and Therapeutically Applicable Research to Generate Effective Treatments, as well as efforts such as the International Cancer Genome Consortium, thousands of tumors of many types have been sequenced. We have learned from these and other studies that pediatric cancers have significantly lower mutational burden than do adult cancers, ranging from 0 to 18 protein coding alterations compared with a median of 44 nonsilent mutations in adult cancers.^1-4 With the lower mutational burden comes fewer actionable genetic alterations (ie, those that permit targeting by an available therapeutic agent). One example is neuroblastoma, where the only currently actionable mutation is ALK, which is mutated in only 9.2% of tumors.²