Concordance of circulating tumour DNA and matched metastatic tissue biopsy in prostate cancer

Targeted sequencing across 72 clinically relevant genes was performed on 45 plasma cell-free DNA samples collected at the time of a metastatic tissue biopsy in men with metastatic castration-resistant prostate cancer, and the alterations were compared with exome sequencing data from the matched tissue. Seventy-five point six per cent of the cell-free DNA samples had a circulating tumour DNA proportion greater than 2% of total cell-free DNA. In those men, all somatic mutations identified in the matched metastatic tissue biopsies were concurrently present in circulating tumour DNA, and the hierarchy of variant allele fractions for shared mutations was closely similar between the two. Copy-number profiles between matched liquid and solid biopsy were highly correlated and individual copy-number calls in clinically actionable genes were 88.9% concordant. Detected alterations included AR amplification in 22 samples, 64.7%, SPOP mutation in 3, 8.8%, and inactivating alterations in TP53, PTEN, RB1, APC, CDKN1B, BRCA2 and PIK3R1. In several men, circulating tumour DNA sequencing revealed changes not present in the paired solid biopsy, including alterations in the androgen receptor, WNT and PI3K pathways.