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. Author manuscript; available in PMC: 2022 Dec 13.
Published in final edited form as: Cancer Cell. 2021 Nov 4;39(12):1643–1653.e3. doi: 10.1016/j.ccell.2021.10.006

Figure 4.

Figure 4.

Genetic, phenotypic, and clinical attributes of N1 DLBCL. A. Distribution of DLBCL gene expression subgroups among NOTCH1-mutant DLBCLs. B. Recurrently mutated genes in NOTCH1-mutant DLBCL. Shown are the type and prevalence of mutations in the indicated genes among NOTCH1-mutant and NOTCH1-wild type DLBCLs. Genes are assigned to functional categories, as indicated. P values are from a Fisher’s Exact Test comparing the prevalence in NOTCH1-mutant and NOTCH1-WT cases. Mut: Non-synonymous mutation; Trunc: Truncating mutation; WT: wild type; ns: non-significant. C. Prevalence of mutations targeting biologic pathways characteristic of N1 DLBCL. Prevalence is based on 1,431 DLBCL NOTCH1-WT and NOTCH1-mutant DLBCL cases for which sequencing data was available for all genes in the indicated pathways. P values are from a Fisher’s Exact Test comparing the prevalence in NOTCH1-mutant and NOTCH1-WT cases. D. Left panel: Average expression of the indicated gene expression signatures in the indicated genetic subtypes in the NCI cohort(Schmitz et al., 2018). Bmem-6: Genes upregulated in memory B and memory B precursors relative to germinal center dark zone and light zone B cell cells (Venturutti et al., 2020); TBL1XR1MutUp-1: Genes up regulated by a TBL1XR1 mutant isoform (Venturutti et al., 2020); BACH2Up-1: Genes upregulated in BACH2+ germinal center light zone cells (Venturutti et al., 2020). Right panel: Average expression of the indicated memory B cell marker genes. ****p<0.0001, ***p<0.001, **p<0.01, *p<0.05. Error bars: SEM. E. Schematic of the BCR-dependent NF-κB pathway showing the prevalence of mutations targeting each pathway component in the N1 (NOTCH1-mutant) and MCD subtypes of DLBCL according to the color scale shown. DAG: diacylglycerol; IP3: inositol triphosphate; Ca++: calcium ion; CBM complex: CARD11-BCL10-MALT1 complex; My-T-BCR: MYD88-TLR9-B cell receptor complex. F. Kaplan-Meier plots of event-free and overall survival in younger (age ≤ 60) and older (age > 60) patients with NOTCH1-mutant DLBCL treated with R-CHOP-like chemotherapy, curated from the published literature.