Cancer: The genomics of childhood cancers

Thousands of childhood cancers have been characterized in detail at the genomic and molecular level. The results, presented in two papers published online in Nature this week, shed light on the causes of childhood cancer, and could aid the development of new therapies.

Stefan Pfister and colleagues identified the various genetic changes that had occurred in 914 young people with 24 molecularly distinct types of cancer, including the most frequent and clinically relevant ones, with an emphasis on tumours of the central nervous system. Mutations in genes involved in the repair of double-stranded DNA breaks were found in all cancer types, and 7% of the patients carried a disease-causing mutation in a candidate cancer predisposition gene. Half of the tumours contained mutations that potentially make them amenable to targeted treatments that either exist already or are currently in development.

Jinghui Zhang and colleagues extended these findings further, focusing not only on DNA, but also on the messages transcribed from it. They analysed DNA changes and sequenced the genomes, exomes and transcriptomes of 1,699 paediatric leukaemia and solid tumours. They identified 142 genes associated with cancer in these paediatric patients, of which only 45% matched those found in similar studies of adult cancers. The authors also found eleven mutational signatures - areas in the genome in which mutational processes have left a distinctive mark - including one attributed to ultraviolet-light exposure.

Together, the studies raise hope - druggable targets do exist - but they also reveal that childhood cancers show many differences to their adult counterparts, a fact that needs to be taken into account as new therapies are developed.

doi: 10.1038/nature25795

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