Comprehensive genomic screening may be warranted on all pediatric cancer patients, not just those with a family history of cancer, according to a new study by the St. Jude Children’s Research Hospital — Washington University Pediatric Cancer Genome Project.
The study, published Nov. 19 in the New England Journal of Medicine, is the most detailed analysis yet of the role germline mutations in genes associated with cancer predisposition play in the development of childhood cancer.
Researchers anticipate 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.
“This paper marks an important turning point in our understanding of pediatric cancer risk and will likely change how patients are evaluated,” corresponding author James R. Downing, MD, St. Jude president and CEO, said in the release. “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.”
Researchers conducted next-generation DNA sequencing of both the tumor and normal tissues from 1,120 pediatric cancer patients and found 8.5% of patients had pathogenic or likely pathogenic mutations of genes within their normal tissue that increase their risk of developing cancer. Until 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.
“The frequency of 8.5% represents our current estimate of the number of pediatric patients with a hereditary cancer predisposition,” Downing said in the release. “This number will likely increase as we learn more about mutations in this class of genes in young cancer patients.”
To accomplish that, St. Jude has initiated a new clinical research study, Genomes for Kids, which incorporates 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 is staffed by 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 one of only a few programs in the world focused on evaluating and managing children and families with known or suspected cancer predisposition, according to the release.
“Our study in the New England Journal of Medicine lays the groundwork to understand the spectrum of cancers and age-specific cancer risks associated with germline mutations in predisposition genes and how best to monitor at-risk patients and families,” co-author Kim Nichols, MD, a member of the St. Jude department of oncology and director of the St. Jude Hereditary Cancer Predisposition Clinic, said in the release.
See an infographic on St. Jude’s research.