Mutational Signatures in Pediatric Cancer

The signatures of mutation in cancer genomes are markers of past mutagen exposure or intrinsic DNA repair defects. Recent studies in childhood cancer have shown that mutational signatures can uncover a tumor’s origin - including whether it arose due to inherited mutation – and point to therapeutic vulnerabilities. In this meeting, we will discuss the enormous potential utility for mutational signatures in childhood cancer, in predicting future outcomes and eligibility to clinical trials, .. continue reading mechanisms for therapy-induced drug resistance, as well as performing “reverse genetics” – understanding the tumor’s past evolutionary trajectory and possible etiology. Knowing that childhood cancers are unique, this meeting’s participants will propose mutational signatures approaches that have been adapted for these patients specifically. This will include focusing on thresholds for detecting underlying mutational signatures, such as mismatch repair and homologous recombination, as well as signatures involving structural rearrangements, which are frequent drivers of childhood cancer malignancy.