Monitoring BRAF and NRAS mutations with cell-free circulating tumor DNA from metastatic melanoma patients

The mutation status of the and genes in tumor tissue is used to select patients with metastatic melanoma for targeted therapy. Cell-free circulating DNA (cfDNA) represents an accessible, non-invasive surrogate sample that could provide a snapshot of the and genotype in these patients. We investigated the feasibility of the Idylla™ assay for detection of and mutations in cfDNA of 19 patients with metastatic melanoma at baseline and during the course of treatment. The cfDNA genotype obtained with Idylla was compared to the results obtained with matched-tumor tissue and to clinical outcome. At baseline, 47% of patients harbored a mutation in their cfDNA. Two months after targeted treatment the mutant cfDNA was undetectable in all patients and 3 were disease-free. Moreover, 15% of patients harbored a mutation that was detected with plasma before treatment. The sensitivity and specificity were 80% and 89% for the status, and 79% and 100% for the status in pretreatment cfDNA compared to results obtained with a tissue test. Due to the small size of the population, no significant correlation was observed between the presence of or mutations in cfDNA and the metastatic tumor load or overall survival. In conclusion, this study demonstrated that evaluation with the Idylla system of the and mutation status in cfDNA may be a surrogate for determination of the and status in tumor tissue.