Objective:

To identify pathogenic or likely pathogenic cancer-predisposition variants in newborns and estimate their association with early-onset cancers.

Approach:

• Study Population: Investigators identified 1,948 pediatric patients born in Michigan from 1987 to 2020 who developed a malignant tumor by age 8 and had archived newborn dried blood spots.
• Genomic Sequencing: Targeted next-generation sequencing was performed on 11 autosomal dominant cancer-predisposition genes.
• Variant Detection: Pathogenic or likely pathogenic germline variants were detected in 7% of the patients (n = 132).

Key Findings:

• RB1 variants accounted for 69 of the detected variants, followed by TP53 (24), SMARCB1 (8), and WT1 (7).
• 130 patients developed tumors associated with the affected gene.
• 1 in 27,000 newborns may develop early-onset solid or brain malignancy with a detected cancer-predisposition variant.
• Patients with detected variants received a cancer diagnosis at a median age of 14 months compared to 32 months for non-carriers.

Limitations:

• The study did not prospectively assess the impact of genomic newborn screening on clinical outcomes.
• Lack of a large comparison cohort of cancer-free newborns tested with identical methods.
• Findings may not be generalizable to populations with different ancestry or demographics.
• The panel included only 11 genes, potentially underestimating the number of genetically at-risk newborns.

Conclusion:

The data support the potential for newborn screening for selected cancer-risk genes, but further prospective research is needed to evaluate clinical and public health effects.

Sources:

• Nature Communications