Extensive and differential platinum chemotherapy mutagenesis in livers of children.

Anna Wenger; Jean-Baptiste Vannier; Henry Lee-Six; Robin Loesch; Giulia Emanuelli; Manas Dave; Mehdi Layeghifard; Andrew R J Lawson; Federico Abascal; Pantelis A Nicola; Taryn D Treger; Toochi Ogbonnah; Conor Parks; Thomas R W Oliver; Jonathan Kennedy; Angus Hodder; Nathaniel D Anderson; Felipe Luz Torres Silva; Mi K Trinh; Thomas Dowe; Marwo Habarwaa; James J Sun; Sergio Assia-Zamora; Miriam Cortes-Cerisuelo; Wayel Jassem; Charlotte Town; Anil Dhawan; Vandana Jain; Karin Straathof; Maesha Deheragoda; I&#xf1;igo Martincorena; Liina Palm; J Ciaran Hutchinson; Tim H H Coorens; Claire Trayers; Mariia Yuneva; Nigel Heaton; Adam Shlien; Yoh Zen; Foad J Rouhani; Sam Behjati

doi:10.1126/science.ady0339

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Extensive and differential platinum chemotherapy mutagenesis in livers of children.

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Abstract

Childhood cancer survivors often experience late adverse effects that may be linked to chemotherapy mutagenesis. We studied chemotherapy mutagenesis in normal pediatric tissues using duplex sequencing (NanoSeq) to enable the detection of mutations from single DNA molecules. We found that platinum chemotherapeutics increased the mutation burdens of normal pediatric tissues to levels seen in adults. In the liver, platinum agents imparted a tissue-specific mutational signature that was absent from other tissues. Gene-focused duplex sequencing revealed that chemotherapy mutagenesis generates a great diversity of nonsynonymous variants, some of which may have functional potential, such as leukemogenic variants in blood. Our findings demonstrate extensive chemotherapy mutagenesis in normal tissues of children, which may provide a plausible link between chemotherapy exposure and adverse effects in later life.

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Child Child, Preschool Humans Antineoplastic Agents Cisplatin Liver Mutagenesis Mutation Organoplatinum Compounds Infant Carboplatin Animals Mice Female Journal Article

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Anna Wenger, Jean-Baptiste Vannier, Henry Lee-Six, Robin Loesch, Giulia Emanuelli, Manas Dave, Mehdi Layeghifard, Andrew R J Lawson, Federico Abascal, Pantelis A Nicola, Taryn D Treger, Toochi Ogbonnah, Conor Parks, Thomas R W Oliver, Jonathan Kennedy, Angus Hodder, Nathaniel D Anderson, Felipe Luz Torres Silva, Mi K Trinh, Thomas Dowe, Marwo Habarwaa, James J Sun, Sergio Assia-Zamora, Miriam Cortes-Cerisuelo, Wayel Jassem, Charlotte Town, Anil Dhawan, Vandana Jain, Karin Straathof, Maesha Deheragoda, Iñigo Martincorena, Liina Palm, J Ciaran Hutchinson, Tim H H Coorens, Claire Trayers, Mariia Yuneva, Nigel Heaton, Adam Shlien, Yoh Zen, Foad J Rouhani, Sam Behjati. 2026-09-10. Extensive and differential platinum chemotherapy mutagenesis in livers of children.. https://doi.org/10.1126/science.ady0339

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