Genome studies shed light on childhood cancers

Two separate genomic studies of childhood cancers reveal differences compared with adult cancers, potentially opening new therapeutic avenues.

The studies, published in Nature, were both 'pan-cancer' analyses of genetic alterations from thousands of childhood tumours.

Childhood cancers had a 14-times lower mutation rate than adult cancers, with most of them arising from a single genetic, cancer 'driver' mutation, found one study. Led by Professor Stefan Pfister at the German Cancer Research Centre in Heidelberg, researchers in this multicentre study, analysed 961 tumours from 24 types of childhood, adolescent and young-adult cancers.

The other study, led by Professor Jinghui Zhang at St Jude Children's Research Hospital in Memphis, Tennessee, analysed the genomes and transcriptomes of 1699 paediatric cancers involving six different types of leukemias and solid tumours. Among the mutational signatures that they discovered, there was a novel one for leukemias, which suggested an association with ultraviolet light exposure.

Both studies confirmed previous findings that paediatric cancers have fewer mutations than adult cancers and that the total number of mutations correlates with increase in age.

Additionally, both studies showed that different genes are mutated in childhood compared with adult cancers. For the types of cancer analysed, only 30 percent of childhood driver mutations overlapped with mutations identified in adult pan-cancer studies from the Heidelberg study and 45 percent from the Tennessee study.    

Professor Zhang said: 'This shows for the first time that paediatric and adult cancers frequently arise from different genes with different mutations… The results really bring home the message that paediatric cancer patients are not small adults and their disease should not be treated as if that were the case.'

These findings pinpoint the need for precision-medicine treatments in childhood cancers. With more than 140 cancer driver genes identified from each of these studies alone, new screening tests and therapies have to be considered.

The Heidelberg study uncovered mutations in genes involved in DNA repair across all the distinct cancer types it analysed and estimated that half of these mutations can be targeted by drugs that are either available or under development.