GSEA of MYC, NOTCH1, and IRF4 target gene sets in the 2 molecular subgroups of cHL identified by unsupervised hierarchical clustering. Top: The overall expression of the target gene sets of the MYC, IRF4, and NOTCH1 transcription factors (composing 469, 76, and 44 genes, respectively) was found by GSEA to be significantly up-regulated in the profiles of microdissected HRS cells belonging to one cHL subgroup (subgroup 2; n = 8 cases) versus the other cHL subgroup (subgroup 1; n = 8 cases) emerging on unsupervised hierarchical clustering (Figure 1; supplemental Figure 4). The 44 NOTCH1 target genes in T-ALL cells are those genes whose promoters are bound by NOTCH1 and are down-regulated on pharmacologic NOTCH1 inhibition in T-ALL lines with mutated NOTCH1.38 Bottom: Heat map of the expression pattern in the individual primary HRS cell samples of the leading-edge genes (ie, those genes most contributing to the enrichment of each gene set: 264 MYC targets, 42 IRF4 targets, and 27 NOTCH1 targets) whose probe sets show ≥ 1.5-fold mean up-regulation in cHL subgroup 2. The color code of the heat map is shown by the bar on the right.
