Fig. 2: Comprehensive profiling of AR genomic alterations in A031201 cfDNA. | Nature Communications

Fig. 2: Comprehensive profiling of AR genomic alterations in A031201 cfDNA.

From: AR alterations inform circulating tumor DNA detection in metastatic castration resistant prostate cancer patients

Fig. 2

a ctDNA aneuploidy fraction estimated by ichorCNA in targeted DNA-seq data from n = 776 cfDNA specimens. Samples below the ctDNA aneuploidy-high threshold of 0.142 are in gray/pink. b Relative AR gene copy number ratio in cfDNA specimens ordered left to right as in (a). A log2 ratio >= 0.3 is considered a gain. c Relative AR upstream enhancer copy number ratio in cfDNA specimens ordered left to right as in (a). A log2 ratio >= 0.3 is considered a gain. d Number of AR gene structural rearrangements (AR-GSRs) in cfDNA specimens ordered left to right as in (a). AR-GSRs predicted to encode AR variant proteins with a truncated ligand binding domain (LBD), and AR-GSRs predicted to be associated with AR amplification on extrachromosomal DNA (ecDNA), are shown. e AR single nucleotide variants (SNVs) detected in cfDNA specimens as in (a). f Scatterplot of relative AR gene copy number ratio and number of AR-GSRs. Dots are colored blue based on copy number gain of the AR gene body. Dark blue denotes samples with 2 or more AR-GSRs and AR gene body copy gain, which is a signature of AR ecDNA (shown also in (d)). ‘n’ refers to the number of patient samples. Forest plots illustrating hazard ratio (squares) and 95% confidence intervals (horizontal lines) for (g) radiographic progression (rPFS) and (h) overall survival (OS) in patients demonstrating indicated cfDNA features. Multivariable analysis is adjusted for ctDNA aneuploidy fraction. P-values are from the Wald test from the Cox’s proportional hazards model, adjusted for multiplicity using the Benjamini-Hochberg method (false discovery rate). A FDR < 0.05 is considered statistically significant. ‘n’ refers to the number of patients. i UpSet plot showing co-occurrence of indicated AR genomic alterations. j Scatterplot of relative AR gene copy number ratio and AR upstream enhancer copy number ratio. Dots are colored based on copy number gain of the AR gene body only (brown), AR upstream enhancer only (gold), or both the AR gene body and AR upstream enhancer (red). ‘n’ refers to the number of patient samples.

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