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Updated: Sep 10, 2026
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Pre-operative circulating tumour DNA in high-risk primary cutaneous melanoma: prospective feasibility in molecular
Magnús Pétur Bjarnason Obinah1, Estrid Høgdall2, Tim Svenstrup Poulsen3
1Department of Plastic Surgery, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Background And Purpose:
Circulating tumour DNA (ctDNA) has emerged as a prognostic biomarker in melanoma, but its detectability in pre-operative blood from patients presenting with primary cutaneous melanoma remains incompletely evaluated. We assessed the feasibility of pre-operative ctDNA detection in high-risk primary melanoma using routinely available methods in molecular pathology.
Patients/Material And Methods:
In a prospective single-institution cohort enrolled between September 2021 and December 2022, pre-operative plasma was obtained from patients with clinically suspected primary cutaneous melanoma. Patients with pathologically confirmed invasive melanoma and high-risk features (≥ T3a, ≥ N1a, or ≥ M1a) were selected for molecular analysis. Tumour tissue was analysed using next-generation sequencing (NGS) to identify targetable BRAF or NRAS driver mutations, and pre-operative plasma was analysed for ctDNA using droplet digital PCR (ddPCR) for BRAF V600E or targeted NGS for other driver mutations.
Results:
Of the 288 consented patients with pre-operative blood samples, 21 met high-risk criteria, and 12 had a targetable BRAF or NRAS driver mutation in tumour tissue and underwent tumour-informed plasma ctDNA analysis. Pre-operative ctDNA was not detected in any of these 12 patients (0 of 12; 95% confidence interval [CI] 0 to 26.5%). All ddPCR and NGS assay controls performed as expected, and wild-type copy counts were consistent across ddPCR samples.
Interpretation:
The finding is concordant with two independent studies using different methods, and a mathematical prediction of ctDNA shedding from small primary tumours. Reliable pre-operative ctDNA detection in primary melanoma may require alternative cell-free DNA (cfDNA) approaches, such as bespoke multivariant or mutation-agnostic methods.
