Relapse of acute lymphoblastic leukemia (ALL) remains a leading cause of childhood cancer-related death. Prior studies have shown clonal mutations at relapse often arise from relapse-fated subclones that exist at diagnosis. However, the genomic landscape, evolutionary trajectories, and mutational mechanisms driving relapse are not completely understood. In an analysis of 92 cases of relapsed childhood ALL incorporating multimodal DNA and RNA sequencing, deep digital mutational tracking, and xenografting to formally define clonal structure, we identified 50 significant targets of mutation with distinct patterns of mutational acquisition or enrichment. The somatic mutation spectrum in ALL at diagnosis and relapse is shown is this heatmap. Only nonsilent mutations in recurrently affected (≥3 cases) key genes (COSMIC Cancer Gene Census or reported leukemia relevant genes) are displayed. Samples are divided into B-ALL (n = 67) and T-ALL (n = 25) arrayed such that diagnostic samples are next to their corresponding relapse sample. Genes are divided into functional groups or pathways. Click here to return to the diagnostic view separated from relapse

Detailed information for each sample can be found here:Supplementary data page