Genomic Analysis of Circulating Tumor DNA Using a Melanoma-Specific UltraSEEK Oncogene Panel.

Abstract

The analysis of circulating tumor DNA (ctDNA) provides a minimally-invasive molecular interrogation that has the potential to guide treatment selection and disease monitoring. Here, we evaluated a custom UltraSEEK melanoma panel for the MassARRAY system, probing for 61 mutations over 13 genes. The analytical sensitivity and clinical accuracy of the UltraSEEK melanoma panel was compared to droplet digital PCR. The blinded analysis of 68 mutations detected in 48 plasma samples from stage IV melanoma patients revealed a concordance of 88% between the two platforms. Further comparison of both methods for the detection of BRAF V600E mutations in 77 plasma samples demonstrated a Cohen's κ of 0.826 (BCa 95% CI 0.669 to 0.946). Our results indicate that the UltraSEEK melanoma panel is as sensitive as ddPCR for the detection of ctDNA in this cohort of patients but highlight the need for detected variants to be confirmed orthogonally to mitigate any false positive results. The MassARRAY system enables rapid and sensitive genotyping for the detection of multiple melanoma-associated mutations in plasma.