Population-based genomic detection of childhood cancer predisposition using newborn dried blood spots.
In a Michigan birth cohort, targeted sequencing of archived newborn dried blood spots identified pathogenic or likely pathogenic variants in 11 cancer-predisposition genes among 6.8% of 1,948 children who developed a solid or central nervous system malignancy by age 8, with strong gene–tumor specificity.
Open original publication →What the AI sees
In a Michigan birth cohort, targeted sequencing of archived newborn dried blood spots identified pathogenic or likely pathogenic variants in 11 cancer-predisposition genes among 6.8% of 1,948 children who developed a solid or central nervous system malignancy by age 8, with strong gene–tumor specificity.
Research significance
The study provides retrospective evidence that selected germline cancer-predisposition variants can be detected at birth; it supports, but does not test, the hypothesis that prospective newborn screening followed by risk-adapted surveillance or prevention could enable earlier diagnosis and improve outcomes.
Source abstract
Population-based genomic newborn screening identifying newborns at risk for early-onset cancers has not been evaluated. Here, within a Michigan birth cohort (1987-2020), we identify all children developing a solid or central nervous system malignancy by age 8 years (n = 1948). We perform targeted sequencing of 11 cancer predisposition genes using archived newborn dried blood spot DNA. We find pathogenic or likely-pathogenic germline variants (P/LP) in 6.8% of cases (n = 132): RB1 (n = 69), TP53 (n = 24), SMARCB1 (n = 8), WT1 (n = 7), RET (n = 6), SUFU (n = 6), PTCH1 (n = 4), DICER1 (n = 4), APC (n = 3) and PHOX2B (n = 1). We show approximately 1/27,000 newborns develop an early-onset malignancy with an associated pathogenic or likely-pathogenic variant. Germline variant prevalence is 100% in medullary thyroid carcinoma, 40% in retinoblastoma, and 11-30% across five additional diagnoses, with strong gene-tumor specificity (p < 0.001). P/LP variants are rare in comparison datasets from healthy newborns and gnomAD. Our data support newborn screening for selected cancer-risk genes.