Fig. 3

Frequent low allele-burden mutations in KMT2C in AML with abn(7). A Lollipop plot depicts the localization and frequency of each KMT2C variant (n = 98, in 78/467 patients, from KMT2C refSeq NM_170606.3). Distribution in the context of Pfam domains was adapted from MutationMapper from cbioportal [64, 65] with information on the overlap of mutations to a statistically significant hotspot in cancer [66] or to reports of functional effects in the oncology knowledge base OncoKB™ [67, 68]. Color codes were used to distinguish types of observed mutations: 72 missense (blue), 16 truncating (red), 4 inframe (yellow), and 6 alterations affecting splice sites (light blue). B Frequency distribution of genomic events affecting the KMT2C locus: SNVs and CNVs lead to a multi-hit classification of 47 KMT2C-mutated patients from the extension cohort (n = 342) into groups according to genomic events present in the locus (1mut, > 1mut and mut + del). C Distribution of the VAF values of KMT2C mutations found for patients in the KMT2C multi-hit groups with at least one mutation present (n = 47). D, E The Odds ratio plot shows a multivariable binomial logistic regression fitted for the (D) ten genes with a P < 0.1 in univariate analysis (Figure S4A) and for (E) the six genes with a P < 0.1 in univariate analysis (Figure S4B). To the left, a bar plot diagram depicts the number of mutated patients: for each of the ten genes included in the multivariate model color-coded by (D) type of AML (de novo AML, blue; sAML, red) and (E) for each of the six genes included in the multivariate model color-coded by abn(7) group [−7, green; del(7q), grey]. To the right, logOR with confidence intervals of 95%, CI, and P values are shown