Signatures of Mutational Processes in Childhood Cancers

Backgrounds: Most cancers arise as consequence of the accumulation of somatic mutations, including specific driver mutations and random passenger mutations. Both represent the imprint of different DNA damage and DNA repair processes interfering with the genome, which can also be referred to as mutational signatures.

Methods: Recently, a method deciphering mutational signatures by modelling the underlying processes as a blind source separation problem was proposed and applied almost exclusively on adult cancers.

Somatic mutations can be extracted from whole genome or whole exome next generation sequencing (WGS/WES) data. We have collected a WGS/WES data set of more than 900 childhood cancers including all relevant entities to subject them to analysis for mutational signatures.

Results: We were able to prove the presence of the previously detected signatures in entities that had been analysed for mutational signatures before and therefore investigated their presence in other pediatric cancers. Additionally, we found evidence for additional signatures unique to childhood cancers.

Conclusion: Unravelling the mutational processes triggering tumorigenesis allows for an estimation of the origins of cancer with a potential impact on understanding cancer aetiology, but also therapy and prevention. A comprehensive analysis of mutational signatures in childhood cancers also sets the basis for a pan-cancer comparison from a novel point of view focusing specifically on the processes behind the visible mutational profiles.