Article Figures & Data
Figures
- Figure 1.
The landscape of putative driver gene mutations in PBL. A, Sample information, MYC translocation, and somatic mutation information are shown for 110 cases of PBL samples. The heatmap represents individual mutations in each sample, color-coded by type of mutation. B–E, Individual gene mutation maps for frequently mutated genes, showing mutation subtype, position, and evidence of mutational hotspots, based on COSMIC database information. Y-axis counts at the bottom of the maps reflect the number of identified mutations in the COSMIC database. F, Sanger validation of single nucleotide variants (SNV) in STAT3 mutants.
- Figure 2.
Recurrent copy number changes in PBL. A, GISTIC 2.0 results showing recurrent copy number changes in PBL samples. The green line indicates q-value = 1.0 × 10−6. B, A zoomed-in view of 11p13 on 17 cases of PBL, which shows consistent focal copy number gains of CD44. The figure was generated by the IGV browser using CNV segment files from SNP-FASST2 algorithm. C, Scatter plot representations of genes located in regions with recurrent copy number gains in PBL (q-value <1.0 × 10−6, GISTIC 2.0). The horizontal axis indicates the −log10(q-value) from the GISTIC report, and the vertical axis is the median gene expression level (normalized RPKM value) from PBL RNA-seq data (n = 20). D, IHC showing strong CD44 protein expression on tumor cells membrane in a representative sample (A10), which has a focal CD44 copy number gain.
- Figure 3.
Comparative analysis of PBL and other B-cell malignancies. A, Unsupervised clustering based on frequencies of the most recurrently mutated genes from PBL, multiple myeloma, CLL, and two main subtypes of DLBCL (Methods). B, Hierarchical clustering of mRNA expression profiles across plasmablastic lymphoma, multiple myeloma, CLL, DLBCL and normal B cells, including centroblast (CB), naïve B (NB), and memory B cells (MB). Note that the JAK–STAT signaling pathway does not appear in this figure because only the top 1,000 most aberrantly expressed genes were selected for this analysis. Functional enrichment analysis was performed using g:profiler.
- Figure 4.
Activation of JAK–STAT pathway in PBL. A, Preranked gene set enrichment analysis indicating the significant positive enrichment of KEGG JAK–STAT signaling pathway in PBL. The preranked gene list was generated on the basis of the median expression level on PBL samples. B, Enrichment comparisons of JAK–STAT pathway between PBL and other B-cell malignancies by performing single-sample GSEA (ssGSEA). Pairwise P values were derived from t test. C and D, IHC plots showing pSTAT3 protein expression in >75% of tumor cells, confirming STAT3 activation in STAT3 mutated cases. Results using anti-pSTAT3 antibody are photographed at ×100 and ×400 magnification.
- Figure 5.
EBV transcription programs in PBL. Heatmap illustrating the full genome expression of EBV in the RNA-seq data of PBL samples (virus gene counts are normalized per million host reads). 16/17 EBV-positive samples show significantly higher expression of lytic genes such as BALF4 (encoding the envelope glycoprotein B) and BALF5 (encoding the DNA polymerase catalytic subunit) compared with the expression of canonical latency programs.
Additional Files
Supplementary Data
- Supplemental Information - Supplemental Fig.S1-S9 and Supplementary Methods
- Supplementary Tables - Supplementary Tables S1-S9
Volume 1, Issue 1
