Figure 3.
DNMT3A-MT PTCL-TBX21 cases are enriched for an activated CD8+ cytotoxic phenotype. (A) Heatmap of differentially expressed genes between DNMT3A-MT and WT PTCL-TBX21 cases. (B) Gene set enrichment analysis (GSEA) for DNMT3A-MT PTCL-TBX21 cases as compared with WT cases. Pathway diagrams containing differentially expressed genes of interest are displayed within shaded regions. (C, top) Representative images of CD4 and CD8 tumor antigen staining in PTCL-NOS cases. Images are taken at identical high-power magnifications. (C, bottom) Bar graph of the frequency of immunohistochemistry positivity for n = 10 PTCL-TBX21 cases with respect to DNMT3A mutation status. (D) Pooled metagene plot for MeDIP-Seq profiles of DNMT3A-MT PTCL-TBX21 cases as compared with WT cases. Lines represent sample-type average log2 (peaks per bp per gene) for indicated regions, and shading represents standard error among samples. (E) Box plots of the log2 ratio (observed/expected) for 5mC peaks within the indicated genomic regions. (F) Heatmap of concordant differentially expressed and methylated genes. (G) University of California, Santa Cruz (UCSC) genome browser visualization of MeDIP-Seq peaks in DNMT3A-MT samples and WT samples for the listed genes. Gene diagrams represent the position of TSS relative to displayed genomic regions. Histograms display median-centered expression of genes of interest. Sequencing and GEP status are denoted by the in-figure key. TSS, transcriptional start site; TTS, transcriptional termination site; MT, mutant.