Fig. 2.

Mutations and SBS signatures found by WES and Targeted Sequencing in the abn(7) exploration and extension cohorts. A Bar graph showing the frequency of mutations identified by WES in patients (n = 60) per gene for genes mutated in ≥ 2 patients. Bars colored dark blue signify genes of particular importance due to high mutation frequency or previously underestimated prevalence in AML. The fraction of mutated patients per gene is shown above each bar (%). B The graph shows the mutational profile extracted from WES, which represents the two main signatures of most samples from the exploration cohort. Sig-A had high cosine similarities to the signatures reconstituted from the components that expectation maximization extracted SBS1/SBS5 in COSMIC (0.939) and SBS1/SBSblood in normal blood cells (0.945)[34, 35]. The bars represent the relative contributions of clustered genome-wide substitutions (SBS, y-axis) for each 96 trinucleotide sequences (x-axis) and distributed across the six possible cytosine or thymine bases substitutions. C Oncoplot showing mutations found in 43 of the 64 genes included in the TS gene panel in 452 patients of the extension cohort (n = 467 patients). According to baseline karyotype information, patients were segregated into two major groups: abn(7)/non-complex karyotype (non-CK, grey) or abn(7)/complex karyotype (CK, red). The marks on the top rows correspond to patients classified by cytogenetic information into having −7 (dark blue) or del(7q) (yellow). FLT3 includes all FLT3 alterations. *In the TS panel, only exons 28–38 of NF1 were investigated. The left bar plot shows the frequency (%) of mutated patients per gene. On the right side, a boxplot shows the statistical difference between the number of mutations found for these groups, median 4 versus 2 respectively for abn(7)/non-CK versus abn(7)/CK (two-tailed t test, n = 467, ****P < 0.0001)