The most detailed analysis yet of the role germline mutations in genes associated with cancer predisposition play in the development of childhood cancer suggests that comprehensive genomic screening may be warranted on all pediatric cancer patients, not just those with a family history of cancer. The study from the St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project appears in the November 19 edition of the New England Journal of Medicine. Ultimately, researchers anticipate that systematic monitoring of patients and family members who have germline mutations in cancer predisposition genes will allow the detection of cancers at their earliest and most curable stage, thereby improving the outcomes for these children and family members.

Researchers conducted next-generation DNA sequencing of both the tumor and normal tissues from 1,120 pediatric cancer patients and found that 8.5 percent of patients had pathogenic or likely pathogenic mutations of genes within their normal tissue that increase their risk of developing cancer. Prior to this study, the presence of such germline mutations in pediatric cancer patients was thought to be extremely rare and restricted to children in families with strong histories of cancer. This study revealed that more than half of the children with germline mutations lacked any family history of cancer. 

"This paper marks an important turning point in our understanding of pediatric cancer risk and will likely change how patients are evaluated," said corresponding author James R. Downing, M.D., St. Jude president and chief executive officer. "For many pediatric cancer patients, comprehensive next-generation DNA sequencing of both their tumor and normal tissue may provide valuable information that will not only influence their clinical management but also lead to genetic counseling and testing of their parents and siblings who may be at risk and would benefit from ongoing surveillance." 

"The frequency of 8.5 percent represents our current estimate of the number of pediatric patients with a hereditary cancer predisposition," Downing added. "This number will likely increase as we learn more about mutations in this class of genes in young cancer patients." To accomplish the latter, St. Jude has initiated a new clinical research study, Genomes for Kids (G4K), which incorporates an unparalleled level of next-generation sequencing into the medical workup of every eligible pediatric cancer patient who enters the hospital for treatment.