Fig. 1. TP53 alterations enrich within GCB-like DNA subclassification alterations and rrDLBCL patients compared to de-novo cohorts. (A) K2 (2-cluster) NMF clustering. rrDLBCL patients (N=127) were analyzed for the best fit when measuring the association patterns of DNA alterations (N=91). Patient similarity is designated by color, with red representing the most co-association and blue the least. The RR1 and RR2 subsets that emerged from clustering are designated by light grey and dark grey coloring, respectively. (B) A volcano plot displays differentially enriched DNA alterations between RR1 and RR2. Comparative marker selection between the groups resulted in 2-sided T and FDR values. Greater T values were associated with RR1 and lesser values with RR2. The dotted line represents the 0.05 FDR threshold to be met for significant association with one family over the other. Significant alterations are color coded for their corresponding LymphGen cluster, if designated. (C) TP53 alterations are significantly enriched towards EZB tumors in rrDLBCL but not in de-novo DLBCL. Stacked bar graphs denote the presence of TP53 alterations within EZB and non-EZB tumors. The pre-treatment Schmitz et al. 2018 [3] cohort is compared to the Rushton et al. [9] rrDLBCL cohort. Significance was determined with a Fisher’s Exact test within both groups. (D) TP53 Alterations significantly co-occur with EZB alterations and significantly occlude MCD alterations. A volcano plot displays TP53 Pearson distance for measured rrDLBCL genes. FDR-corrected correlation similarity values are plotted on the Y-axis, with FDR <0.05 noted with a dotted line. Genes are labelled and noted for LymphGen subclassification. (E) RR2 driver genes increased association with TP53 alterations in comparison to pre-treatment association measurements. Z-score normalized Pearson Distance values are plotted on the Y-axis against RR1 and RR2 genes on the X-axis. rrDLBCL associations (Rushton) are compared to 3 separate de-novo cohort values (Lacy, Reddy, and Wright) based on TP53 co-association. Two-way ANOVA analysis was used to measure significance between pre-treatment and rrDLBCL values after Bonferroni multiple comparison correction.

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