Extensive and differential platinum chemotherapy mutagenesis in livers of children | Science

Duplex sequencing (NanoSeq) of normal liver tissue from childhood cancer survivors revealed extensive and highly differential mutagenesis caused by platinum-based chemotherapy, providing a direct molecular link between treatment exposure and late adverse effects. The study found that platinum agents leave a distinctive mutational signature in pediatric hepatocytes that differs markedly from age-related background mutation accumulation. These findings, published in Science, offer a mechanistic explanation for the elevated risk of secondary malignancies and organ damage observed in long-term survivors of childhood cancer, and may inform future strategies to mitigate chemotherapy-induced genomic damage.