Figure 2.
Myd88-driven mouse models display genomic and transcriptomic features reminiscent of human ABC-DLBCL. (A) A heat map was generated from genes expressed differentially between the individual pairs of genotypes. The normalized DeSeq2 counts were centered after a row-wise mean subtraction. Highlighted MGI Gene Symbols were extracted from the Hallmark NfkappaB signature, Jensen compartments of NfkappaB, Jensen B-cell receptor (BCR) complex, and WikiPathways BCR, which were also significantly enriched in cluster 1. The right panel shows dot plots of significantly altered gene sets within cluster 1 and cluster 2, respectively. The size of the dot corresponds to the number of genes overlapping between the given cluster and the gene set, whereas the adjusted P value is visualized following a color code with an individual legend being provided. Gene sets highlighted in the heat map are marked in red color (n = 60). (B) Murine lymphoma transcriptomes were clustered by the expression of genes included in a published set of gene signatures specific to different GC developmental stages; DZ, dark zone; Int, intermediate; LZ, light zone; PreM, prememory; PBL, plasmablast. (C) Flow cytometric analyses of lymphoma samples for the expression of memory (CD38+/Fas–, gate “MB”) and germinal center B cell (CD38–/Fas+, gate “GCB”) surface markers. The expression levels of CXCR4 and CD86 were determined to distinguish between light and dark zone profiles (gates “LZ” and “DZ”). Splenocytes from Cd19Cre/wt were used as a reference. One case representative of 9 analyzed 79-PPMBC tumors is illustrated, the full set of cases is visualized in supplemental Figure 2E-F. (D) The abundance of memory B cells across different genotypes was quantitatively estimated using mMCP-counter, a method that uses a proprietary score to estimate the abundance of specific cell types (n = 60). (E) Oncoplot from MBC, 79-MBC, PPMBC, and 79-PMBC lymphomas (n = 65). Displayed are recurrently mutated genes identified using OncodriveCLUST,29 a method specifically designed to identify significantly mutated genes that are subject to positive selection in cancer. These genes have been implicated in MCD DLBCL, as indicated by the “mut. in MCD” label. Moreover, mutations that are significantly enriched in any of the investigated genotypes are depicted. IL-2, interleukin 2; PDT, photodynamic therapy; TNF, tumor necrosis factor.

Myd88-driven mouse models display genomic and transcriptomic features reminiscent of human ABC-DLBCL. (A) A heat map was generated from genes expressed differentially between the individual pairs of genotypes. The normalized DeSeq2 counts were centered after a row-wise mean subtraction. Highlighted MGI Gene Symbols were extracted from the Hallmark NfkappaB signature, Jensen compartments of NfkappaB, Jensen B-cell receptor (BCR) complex, and WikiPathways BCR, which were also significantly enriched in cluster 1. The right panel shows dot plots of significantly altered gene sets within cluster 1 and cluster 2, respectively. The size of the dot corresponds to the number of genes overlapping between the given cluster and the gene set, whereas the adjusted P value is visualized following a color code with an individual legend being provided. Gene sets highlighted in the heat map are marked in red color (n = 60). (B) Murine lymphoma transcriptomes were clustered by the expression of genes included in a published set of gene signatures specific to different GC developmental stages; DZ, dark zone; Int, intermediate; LZ, light zone; PreM, prememory; PBL, plasmablast. (C) Flow cytometric analyses of lymphoma samples for the expression of memory (CD38+/Fas–, gate “MB”) and germinal center B cell (CD38–/Fas+, gate “GCB”) surface markers. The expression levels of CXCR4 and CD86 were determined to distinguish between light and dark zone profiles (gates “LZ” and “DZ”). Splenocytes from Cd19Cre/wt were used as a reference. One case representative of 9 analyzed 79-PPMBC tumors is illustrated, the full set of cases is visualized in supplemental Figure 2E-F. (D) The abundance of memory B cells across different genotypes was quantitatively estimated using mMCP-counter, a method that uses a proprietary score to estimate the abundance of specific cell types (n = 60). (E) Oncoplot from MBC, 79-MBC, PPMBC, and 79-PMBC lymphomas (n = 65). Displayed are recurrently mutated genes identified using OncodriveCLUST,29 a method specifically designed to identify significantly mutated genes that are subject to positive selection in cancer. These genes have been implicated in MCD DLBCL, as indicated by the “mut. in MCD” label. Moreover, mutations that are significantly enriched in any of the investigated genotypes are depicted. IL-2, interleukin 2; PDT, photodynamic therapy; TNF, tumor necrosis factor.

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