Mutational signatures and structural variants in lymphomas derived from IEI patients. (A) Mutational signatures of IEI-lymphoma genomes. Each signature is displayed according to the 96 substitution classifications defined by the substitution class (shown in different colors) and sequence context immediately 3′ and 5′ to the mutated base. The 96 possible mutated trinucleotides are located on the x-axis, and the frequency of the mutation type is shown on the y-axis. (B) Hierarchical clustering of IEI lymphomas based on the percentages of mutational signatures. DNA repair-related somatic and germline mutations identified in each tumor are shown below. (C) Percentages of specific types of somatic indels in PL4 and PL17. (D) SV of WGS-sequenced IEI lymphomas. (E) Comparison of the location of SV breakpoints at early and late replication sites between IEI and non-IEI patients. BER, base excision repair; DDR, DNA damage response; LIG4, LIG4 syndrome; MMR, mismatch repair; NER, nucleotide excision repair; NHEJ, nonhomologous end joining.