A study conducted at St. Jude Children’s Research Hospital (TN, USA) and Washington University (MO, USA) has reported that genetic predisposition may play a significant role in the development of childhood cancer. The research, published in The New England Journal of Medicine, represents the most detailed analysis ever conducted of germline mutations and their association with pediatric cancer.
These results suggest that future comprehensive genomic screening and monitoring of patients and families with germline mutations in cancer predisposition genes could improve patient outcomes.
Next-generation DNA sequencing of tumor and normal tissues was conducted in 1120 pediatric cancer patients. Up until this point, the presence of germline mutations in pediatric cancer patients was thought to be rare and the frequency of patients with hereditary cancer predisposition genes was largely unknown.
Investigators revealed that 8.5% of the patients – almost one in 10 – were born with genetic mutations that increased their cancer risk.
James R Downing, corresponding author and St. Jude President and Chief Executive Officer commented: “This paper marks an important turning point in our understanding of pediatric cancer risk and will likely change how patients are evaluated.
He continued: “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.”
St. Jude has initiated Genomes for Kids, a new clinical research study that is incorporating next generation-DNA sequencing into the clinical management of every eligible pediatric cancer patient. This research will enable investigators to learn more about the frequency of these predisposing mutations and subsequently guide future treatment.
Children who are reported to have a germline mutation in a cancer predisposition gene will be referred to St. Jude Hereditary Cancer Predisposition Clinic. A team of doctors, nurses and genetic counselors then work with families to support the child and determine whether the cancer is inherited.
Richard K Wilson, co-author and Director of the McDonnell Genome Institute at Washington University School of Medicine, concludes: “Now, using genome sequencing, we can see the contribution of germline mutations to pediatric cancer risk. Our results explain why children, who have not lived long enough to accumulate a critical number of cancer-causing mutations can still develop cancer.”
Sources: Zhang J, Walsh MF, Wu G et al. Germline mutations in predisposition genes in pediatric cancer. New England Journal of Medicine. DOI: 10.1056/NEJMoa1508054 (2015); St Jude Children’s Hospital press release