Feasibility of monitoring advanced melanoma patients using cell-free DNA from plasma

Summary

To determine the feasibility of liquid biopsy for monitoring of advanced melanoma patients, cell-free DNA was extracted from plasma for 25 Stage III/IV patients, most (84.0%) having received previous therapy. DNA concentrations ranged from 0.6 to 390.0 ng/mL (median=7.8 ng/mL), and were positively correlated with tumor burden as measured by imaging (Spearman rho=0.5435, p=0.0363). Using ultra-deep sequencing for a 61-gene panel, one or more mutations were detected in 12 of 25 samples (48.0%), and this proportion did not vary significantly for patients on or off therapy at time of blood draw (52.9% and 37.5% respectively; p=0.673). Sixteen mutations were detected in 8 different genes, with the most frequent mutations detected in BRAF, NRAS, and KIT. Allele fractions ranged from 1.1% to 63.2% (median=29.1%). Among patients with tissue next-generation sequencing, 9 of 11 plasma mutations were also detected in matched tissue, for a concordance of 81.8%.

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