Paediatric cancers are rare, and the development of unrelated, second cancers without known germline predisposing variants, which occur years after a child is cured of their first cancer, is even rarer. Sánchez-Guixé et al. investigated the possible routes to these second malignancies by studying four such clinical cases.

In adults with tAML, exposure to chemotherapy leads to a mutagenic and/or cancer-promoting effect in which a full clonal expansion from a single hematopoietic stem cell occurs. Since chemotherapeutic drugs, in particular platinum-based drugs, leave a mutational footprint in the genome, the authors could determine that the childhood secondary AML in this case also arose after exposure to cytotoxic drugs.