1. Ewing sarcoma tumors acquire somatic aberrancies with treatment.
Ewing sarcoma tumors acquire somatic aberrancies with treatment. A, coding mutations in 24 Ewing sarcoma tumor samples identified from WES and WGS of patient tumors and paired normal tissue with available clinical data. Bars indicate the number of coding-region mutations in each tumor and are grouped by disease state (diagnostic or treated) and ordered by number of mutations (high to low) within each group. B, the rate of coding mutations is higher in tumors sequenced after treatment than in tumors from diagnostic samples. Plotted are the average mutation rates for diagnostic and treated samples ± the standard deviation (SD), P = by Mann–Whitney test. C, treated tumors have a lower fraction of *CpG to T transitions and a higher fraction of substitutions at cytosines in TpC dinucleotides. The NpN nomenclature indicates the dinucleotide sequence involved in the indicated mutation and * indicates the mutated base. Plotted are the fractions of SNVs for each mutational category ± the 95% CI; *, P < 0.05; **, P < 0.01 by z test. D, shown is the rate of SNVs by 3-base context from tumors acquired at diagnosis (left) or after treatment (right). Colors indicate the single-nucleotide change, and the location of each bar in the matrix indicates the flanking bases. E and F, circos plots of seven tumors sequenced by WGS. Chromosomes displaying cytobands are arranged end-to-end in the outer ring with the inner ring showing segmented copy-number variations generated from exome sequencing. Interchromosomal rearrangements are displayed as purple arcs and intrachromosomal as green arcs. Rearrangements at t(21;22)(q22;q12) in SJDES010 and SJDES018-R indicate the EWS–ERG fusions in these samples. All other tumors demonstrate a translocation at t(11;22)(q24;q12), consistent with the EWS–FLI fusion.
Brian D. Crompton et al. Cancer Discovery 2014;4:
©2014 by American Association for Cancer Research