Figure 2. CDK12-mutant prostate cancer is a novel molecular subtype of mCRPC.
(A) Mutual exclusivity of CDK12 loss, ETS fusions, mismatch repair deficiency (MMRD), SPOP mutations, and homologous recombination deficiency (HRD).
(B) Number of significantly differentially expressed genes (DEGs) for the prostate tumors with different primary genetic drivers.
(C) Enrichment plot for signatures of up- (top) and downregulated (bottom) genes in CDK12 mutant tumors. Genes are ranked by their fold change following siCDK12 knockdown in LNCaP cells, with CDK12-loss signature genes indicated as black dashes. The increased relative frequency (enrichment score) of genes at either end of this spectrum is shown as a blue line.
(D) Heatmap of the top DEGs in CDK12-mutant prostate cancer. Differential expression for all samples (columns) in this heatmap is relative to tumors that are wild-type for primary genetic drivers of prostate cancer (as in B).