Comprehensive Analysis of Transcriptome Variation Uncovers Known and Novel Driver Events in T-Cell Acute Lymphoblastic Leukemia (original) (raw)
Figure 4
Validation and discovery using gene expression data, and SUZ12 ATE.
(A) Classification of the samples using the TFs that are known to be overexpressed in T-ALL. Using the expression patterns of TAL1, TLX1, TLX3, NKX2-5, LYL1 and LMO2 we could discriminate the samples in to six distinct clusters. The heatmap is plotted with the normalized log2(count) values. Gene set enrichment analysis curves are displayed for (B) enrichment of TAL1 associated clusters 2, 6 and 3 in TAL1 based ranking, (C) enrichment of TLX associated clusters 7 and 8 in TLX based ranking, and (D) enrichment of LYL1 associated clusters 10 and 11 in LYL1 based ranking of the genes. (E) Expression of JAK3 and PTK2B across samples is significantly correlated (with PTM p-value = 1E-05). (F) Normalized expression values of TAL1 and TLX1 with translocations affecting these genes indicated. The samples with a translocation have elevated expression of the affected gene, showing the driver potential of the fusion event. There are additional samples with high expression of TLX1 and TAL1 without the indicated fusions, pointing to other mechanisms of activating these genes. (G) Predicted SUZ12 transcript aligned with the known SUZ12 isoforms. Dotted red box indicates the location of the exon-skipping event. (H) The sashimi plot shows the junction (in black) supporting the exon-skipping event in patient sample R5 with respect to Thymus. (I) Agarose gel electrophoresis of the RT-PCR products for validation of SUZ12 exon skipping event. The two isoforms are clearly detected in R5 and to a minor extent in the other T-ALL samples while Thymus shows only the canonical transcript.