Palm, L. | bioRxiv Science

bioRxiv2026

Embryonic origin of cancer in newborn twins

Studying monozygotic twins who present with identical cancers informs on the developmental origins of childhood tumours. Here, we performed whole genome sequencing on multiple tumour, normal, and placental samples to reconstruct the phylogeny of a soft tissue cancer that spread in utero between monozygotic twins. This generalisable and scalable approach allows us to dissect the earliest stages of twinning, revealing unexpected asymmetrical contributions of embryonic lineages to the placenta and each twin.

cancer biology↗

bioRxiv2025

Extensive and differential platinum chemotherapy mutagenesis in children

Childhood cancer survivors often develop long-term adverse effects, which may be caused by direct mutagenesis of cytotoxic agents. Some of these agents generate distinctive DNA imprints (mutational signatures), as exemplified by platinum chemotherapeutics. Here, we examined chemotherapy mutagenesis in paediatric tissues by deploying a duplex sequencing method (NanoSeq), which enables mutation calling from single DNA molecules. We surveyed whole genomes of paediatric liver, blood and other tissues, obtained from surgical resections and at post-mortem. Platinum signatures pervaded all tissues extensively, elevating mutation burdens of paediatric tissues to levels seen in adults. Remarkably, we found a tissue-specific mutational signature in the liver. We examined the functional potential of mutations by gene focused NanoSeq, which revealed that platinum agents cause a vast repertoire of cancer causing variants across normal tissues, such as leukaemogenic mutations in blood. This finding may conceivably link cancer treatment in childhood to mutation-driven long term sequelae.

cancer biology↗