Childhood Chemotherapy Leaves Adult Levels of Mutations in Healthy Tissue

Platinum chemotherapy given in childhood raised the number of mutations in children's healthy tissue to the levels normally seen in adults, a team at the Wellcome Sanger Institute, the University of Cambridge, the Francis Crick Institute and King's College London reports in Science.

The group was looking for the origin of the health problems that childhood cancer survivors often develop years after treatment. Its paper, published Sept. 10, states that the mutations it counted "may provide a plausible link between chemotherapy exposure and adverse effects in later life." A mutation burden is a count of DNA changes carried by healthy cells. It is not a diagnosis, and the authors present the link as plausible rather than demonstrated.

The counting was done with duplex sequencing, a technique that reads both strands of a single molecule of DNA. That, the paper says, is what makes it possible to detect mutations one molecule at a time, rather than only where many cells carry the same change. In the liver, the authors report, platinum drugs left a distinctive pattern of DNA changes that was absent from the other tissues examined.

A second, gene-focused round of the same sequencing turned up what the authors call a great diversity of variants that change the proteins genes code for. Among them, in blood, were leukemia-associated variants that the team says may have functional potential, meaning they could alter how a cell behaves. The study counts mutations in tissue; it does not follow what later happens to the children who carry them.

The work was led by Anna Wenger of the Wellcome Sanger Institute and the University of Gothenburg, with Sam Behjati of the Sanger Institute and the University of Cambridge as senior author, and colleagues. The paper, "Extensive and differential platinum chemotherapy mutagenesis in livers of children," lists Wellcome, Cancer Research UK and the Medical Research Council among its funders.