Tumor DNA from ocular liquids from UM patients

Metastatic risk stratification is critical for uveal melanoma (UM) management. Prognostication for patients currently relies on availability of tumor tissue. Liquid biopsy using cell-free DNA (cfDNA) offers a less invasive alternative, but blood-derived cfDNA shows limited utility in UM due to low tumor DNA fractions. This study investigates the potential of aqueous humor (AH) and vitreous body (VB) aspirates as alternative sources of tumor DNA for molecular prognostication in UM patients at time of diagnosis. In this prospective study, AH and/or VB samples were collected from 96 UM patients. DNA was extracted from the ocular fluids and analyzed via deep amplicon sequencing targeting mutations in GNAQ and GNA11, achieving an average read depth of 120,000, enabling highly sensitive detection of tumor-specific variants. Tumor DNA was detected in AH or VB in 49% of patients, with variant allele fractions (VAFs) ranging from 0.3% to 50%. Tumor DNA was identified in VB only (22 patients), AH only (5 patients), or both (16 patients). Importantly, tumor DNA in AH was almost exclusively observed in patients with monosomy 3. Liquid biopsy of AH and VB is a promising, minimally invasive source for biomarkers enabling risk stratification and informed personalized treatment strategies for UM patients.