Comprehensive genomic screening may be warranted for all pediatric patients with cancer, not just those with a family history of cancer. The finding comes from a detailed analysis of the role germline mutations in genes associated with cancer predisposition play in the development of childhood cancer (N Engl J Med. doi:10.1056/NEJMoa1508054).

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 from the St. Jude Children’s Research Hospital in Memphis, Tennessee, and from the Washington University Pediatric Cancer Genome Project in St. Louis, Missouri, conducted next-generation DNA sequencing of both the tumor and normal tissues from 1120 pediatric cancer patients. They found that 8.5% of patients had pathogenic or likely pathogenic mutations of genes within their normal tissue that increase their risk of developing cancer.

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In this study, the frequency of germline mutations in cancer predisposition genes varied by the type of cancer the child had. The highest frequency, 16.7%, was found in children with non-central nervous system (CNS) solid tumors, followed by CNS tumors, 9%; and leukemia, 4.4%.

The results of this study explain why children, who have not lived long enough to accumulate a critical number of cancer-causing mutations can still develop cancer, stated coauthor Richard K. Wilson, PhD, of Washington University School of Medicine.

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, MD, president and chief executive officer at St. Jude Children’s Research Hospital. “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% 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.

Any child found to have a germline mutation in a cancer predisposition gene will be referred to the new St. Jude Hereditary Cancer Predisposition Clinic, which evaluates and cares for children who are at increased genetic risk for cancer. The clinic staff includes a team of doctors, nurses, and genetic counselors who work with families to determine if a child’s cancer might be inherited. The staff then collaborates with other St. Jude doctors and researchers to find new and better ways to help families with an elevated cancer risk. This new clinic is 1 of only a few programs in the world focused on evaluating and managing children and families with known or suspected cancer predisposition.