Distinct SBS signatures and the occurrence of kataegis-like clustered hypermutation profiles in Vk∗MYC:Wwox KO BM and PBTs. (A) Heat map displaying the most frequent SBS mutational signatures identified in BM PCs and Vk∗MYC:Wwox KO PBPs. The y-axis represents the distinct SBS signatures detected in these samples, whereas the x-axis denotes the individual samples. Each column represents an individual mouse, grouped as indicated at the top of the heat map. In the Vk∗MYC:Wwox KO-PBT group, the first column represents PBL, whereas the remaining 3 columns represent PBPs. Color intensity on the heat map indicates the strength of association with each SBS signature. (B) Rainfall plots of all the mutations across the genome of representative samples from Vk∗MYC:Wwox KO BM and PBTs demonstrating a widespread distribution of clustered hypermutations resembling kataegis. The y-axis represents the distance of each mutation from the preceding mutation. Different colors represent the different types of the mutation substitutions. Clustering of mutations closer to the x-axis indicates a smaller distance between mutations, reflecting hypermutation. (C) Bar graphs illustrating the average normalized counts of Aicda and Apobec2 messenger RNA expression in Vk∗MYC:Wwox WT (n = 5), HET (n = 3), KO (n = 5) BM and Vk∗MYC:Wwox KO PBT (n = 4) samples. Each data point represents the expression level for an individual mouse, with error bars indicating the mean ± standard error of the mean. The green data point indicates Aicda and Apobec2 expression in the Vk∗MYC:Wwox KO1-PBT (PBP), whereas the red data point indicates expression in the Vk∗MYC:Wwox KO4-PBT (PBL). A marked difference in expression was observed; statistical analysis using 1-way analysis of variance did not reach significance, likely due to intersample variability (P = .2646 for Aicda; P = .2680 for Apobec2).
Figure 6.

Distinct SBS signatures and the occurrence of kataegis-like clustered hypermutation profiles in Vk∗MYC:Wwox KO BM and PBTs. (A) Heat map displaying the most frequent SBS mutational signatures identified in BM PCs and Vk∗MYC:Wwox KO PBPs. The y-axis represents the distinct SBS signatures detected in these samples, whereas the x-axis denotes the individual samples. Each column represents an individual mouse, grouped as indicated at the top of the heat map. In the Vk∗MYC:Wwox KO-PBT group, the first column represents PBL, whereas the remaining 3 columns represent PBPs. Color intensity on the heat map indicates the strength of association with each SBS signature. (B) Rainfall plots of all the mutations across the genome of representative samples from Vk∗MYC:Wwox KO BM and PBTs demonstrating a widespread distribution of clustered hypermutations resembling kataegis. The y-axis represents the distance of each mutation from the preceding mutation. Different colors represent the different types of the mutation substitutions. Clustering of mutations closer to the x-axis indicates a smaller distance between mutations, reflecting hypermutation. (C) Bar graphs illustrating the average normalized counts of Aicda and Apobec2 messenger RNA expression in Vk∗MYC:Wwox WT (n = 5), HET (n = 3), KO (n = 5) BM and Vk∗MYC:Wwox KO PBT (n = 4) samples. Each data point represents the expression level for an individual mouse, with error bars indicating the mean ± standard error of the mean. The green data point indicates Aicda and Apobec2 expression in the Vk∗MYC:Wwox KO1-PBT (PBP), whereas the red data point indicates expression in the Vk∗MYC:Wwox KO4-PBT (PBL). A marked difference in expression was observed; statistical analysis using 1-way analysis of variance did not reach significance, likely due to intersample variability (P = .2646 for Aicda; P = .2680 for Apobec2).

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