Sequencing-Based Newborn Screening Identifies Pediatric Cancer Risk at Birth

As a result, cancer predisposition syndromes may remain undetected until symptoms or tumors emerge. Earlier identification could enable surveillance aimed at detecting cancers sooner and potentially reducing treatment intensity. A new study shows that sequencing-based genomic newborn screening can identify some infants at high risk of early-onset cancers.

Researchers at Mass General Brigham, working with the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, evaluated genomic newborn screening using DNA sequenced from standard heel-stick dried blood spots. The approach identifies pathogenic or likely pathogenic variants in genes associated with pediatric cancer predisposition and uses samples already collected about 24 hours after birth. Newborns found to carry these variants could then enter established surveillance programs aimed at detecting cancer earlier.

In a large population-based analysis, investigators examined archived newborn dried blood spots from 1,948 children born in Michigan who later developed a solid or brain tumor by age 8. Sequencing of an 11-gene panel associated with pediatric cancer predisposition syndromes identified pathogenic or likely pathogenic variants in 132 children, representing nearly 7% of the cohort.

In 130 of the 132 children with detected variants, the affected gene was associated with the tumor type that later developed. All six children who developed medullary thyroid carcinoma carried germline RET variants, while 40% of children with retinoblastoma had germline RB1 mutations. Among children with choroid plexus carcinoma, adrenocortical carcinoma, pineoblastoma, or medulloblastoma, 11% to 30% carried a detectable mutation in one of the genes included in the panel.

Children with cancer predisposition variants were also diagnosed substantially earlier than others in the cohort, at a median age of 14 months compared with 32 months. Based on the findings, the researchers estimate that approximately 1 in 27,000 newborns would develop an early-onset cancer that could potentially be predicted through genomic screening, a frequency comparable to some disorders already included in newborn screening programs. They further estimate that such screening could identify about 1,000 children in the U.S. each year who may benefit from earlier surveillance, diagnosis, and treatment.

Retinoblastoma provides an example of the potential clinical value of this approach. Among 69 children with RB1 mutations, 68 later developed retinoblastoma. Within the retinoblastoma group, children with a germline RB1 mutation were diagnosed at a median age of 9 months, compared with 23 months among those without the mutation. Identifying affected infants at birth could enable regular eye examinations to detect tumors sooner, potentially improving vision outcomes while reducing the need for more intensive interventions such as enucleation, chemotherapy, or radiation.

The study, “Population‑based genomic detection of childhood cancer predisposition using newborn dried blood spots,” was published in Nature Communications on August 12, 2026. The teams are working to implement DNA sequencing workflows in public health newborn screening and to channel identified newborns into clinical surveillance protocols.

“Genomic newborn screening, the sequencing of DNA extracted from heel-stick samples, provides a platform for identifying children at high risk for early cancer in order to institute vetted surveillance protocols. Through the collaboration of newborn screening programs, geneticists and oncologists, preventive care can be provided to children who would otherwise remain undiagnosed until symptoms of their cancer developed,” said Richard B. Parad, MD, MPH, director of the Neonatal Genomic Medicine Program in the Mass General Brigham Department of Pediatrics.

“I take care of families who carry genes associated with increased risks of childhood cancer—they have a predisposition syndrome that ‘runs’ in the family. When a new baby is born in that family, we test the child. If that child has the familial mutation, my job is to make sure that if that child develops a tumor, or even a pretumor, we catch it early, which may allow for less toxic therapies and better outcomes,” said Lisa Diller, MD, vice chair of pediatric oncology at Dana‑Farber Cancer Institute.

Related Links
Mass General Brigham
Dana‑Farber/Boston Children’s Cancer and Blood Disorders Center