Enrichment of a novel mutational signature. Mutation signatures associated with relapse were identified with the SomaticSignatures R package28 using non-negative matrix factorization. To account for the association of MAF translocations with the “APOBEC signature,” we differentiated between cases assigned to the MF molecular subgroups (MF) and other cases (noMF). The mutational spectra at presentation and relapse are shown in (A) and (B) for all MF and noMF cases, respectively. For the identification of signatures, only paired samples with at least 30 acquired mutations at relapse were included (6 MF, 16 non-MF cases). (C) The 3 identified signatures are presented. (D) Shown are the contribution of these signatures to the mutation load at presentation (P) and acquired mutations at relapse (R) in the 22 analyzed cases.