Evaluation of Circulating Tumor DNA as a Liquid Biomarker in Uveal Melanoma

• DOI: 10.1167/iovs.65.2.11
• Publication Date: 2024-02-06T18:07:38Z
• Authors: Daniel P. de Bruyn; Natasha M. van Po...; Tom Brands; Susanne C. van de...; Ellis Eikenboom; Anja Wagner; Monique M. van Ve...; Geert Geeven; Berna Beverloo; Caroline M. van Rij; Robert M. Verdijk; Nicole C. Naus; Mette M. Bagger; Jens F. Kiilgaard; Annelies de Klein; Erwin Brosens; Emine Kiliç
• Keywords: Circulating tumor DNA

Purpose: Uveal melanoma (UM) has a high propensity to metastasize. Prognosis is associated with specific driver mutations and copy number variations (CNVs), but limited primary tumor tissue available for molecular characterization due eye-sparing irradiation treatment. This study aimed assess the rise in circulating DNA (ctDNA) levels UM evaluate its efficacy CNV-profiling of patients UM. Methods: In pilot study, we assessed ctDNA blood (n = 18) at various time points, including diagnosis 13), during fractionated stereotactic radiotherapy (fSRT) treatment 6), upon detection metastatic disease 13). Shallow whole-genome sequencing (sWGS) combined silico size-selection was used identify prognostically relevant CNVs 26) from peripheral retrieved 9), fSRT 5), post-treatment follow-up 4), metastasis 4). Results: A total 34 had analyzed and/or CNV analysis points. At diagnosis, 5 13 (38%) detectable (median 0 copies/mL). Upon disease, detected 10 (77%) showed increased 24 copies/mL, P < 0.01). Among six fSRT, three (50%) baseline undetectable ctDNA. During regimen, remained unchanged (P > 0.05). The fractions were low localized sWGS did not elucidate chromosome 3 status samples. However, 7 (70%) metastases, loss corresponded metastatic-risk class. Conclusions: observed harboring metastases suggests potential utility profiling. These findings highlight using patient inclusion therapeutic studies targeting