Figure 2. DACH1 deletion PCa enhances AR signaling.

(A). Interrogation of human PCa gene expression data [26], showing candidate genetic drivers ERG, ETV1/ETV4/FLI1, SPOP, FOXA1, and unknown. Samples with DACH1 homozygous (deep) genetic deletions (29/333) are shown as an additional subtype. The AR score (the average of the AR target gene expression) refers to a group of AR-responsive genes[26], and together with the expression Z-score of the AR target genes, are shown as colorimetric scales. The AR score-based gene names are shown. The androgen receptor (AR) activity, inferred by the induction of AR target genes, was increased in DACH1 homozygous (‘deep’) deletion PCa compared with normal (P=2×10⁻⁵ by t-test) and ERG mutation groups (P=0.003 by t-test). (B). AR mRNA and AR protein levels, shown for each DACH1 deletion sample, were not significantly different. (C). The iCluster[29], mRNA cluster, and SCNA (somatic copy-number alteration), and DNA methylation status are shown for the PCa classified by the corresponding gene deletion subtypes. (D). DACH1 homozygous deletions were enriched for iCluster 2 and 3[29], mRNA cluster 2 (P=0.0003 by Fisher exact test, SCNA (“more” somatic copy-number alteration, P=0.0004 by Fisher exact test), but not for DNA methylation.