Fig. 2: Cancer signatures and mutation loads of RUNX1^mut patients highlight the contribution of AID/RAG pathway to mutagenesis.

a Normalized weights of trinucleotide signatures in four RUNX1^mut BP and four RUNX1^wt patients highlighted the major contribution of signature-9 (related to AID/RAG pathway) in RUNX1^mut BP patients. Weights of the three most frequent signatures (if applicable) in each cancer type are shown across cancers as separate signatures. Total weight of all other signatures is shown under the category “other.” b Expression levels (CPM log₂ values) of RAG1, RAG2, and DNTT genes are significantly higher in RUNX1^mut patients compared with RUNX1^wt patients (*p < 0.05, **p < 0.01, ***p < 0.005, two-tailed student’s test). c Normalized weights of trinucleotide signatures from combined data including 7 RUNX1^mut and 13 RUNX1^wt BP-CML patients underscored the association of signature-9 with RUNX1^mut in BP-CML patients. Weights of the three most frequent signatures in each cancer type are shown across cancers as separate signatures. Total weight of all other signatures is shown under the category “other.” d RAG-RSS heptamer sequence identified by agnostic motif search using MEME in 23/32 breakpoints in RUNX1^mut BP (E value = 1.7 × 10^–14) and in 16/39 breakpoints in RUNX1^wt patients (E value = 1.4 × 10^–14) within 20 bp of breakpoint junctions. e RAG canonical RSS, heptamer, and nanomer sequences (in boxes) separated by 12-bp spacer, identified by agnostic motif search using MEME in 16/32 breakpoints in RUNX1^mut BP within 100 bp of breakpoint junctions (E value = 8.0 × 10^–46).