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Early molecular characterisation of primary tumours is crucial to identify those at risk of metastatic dissemination. Although tumour biopsies are being taken, liquid biopsies of ocular fluids may form a less invasive but relatively unexplored alternative. In this study, we aim to evaluate the DNA content of vitreous fluid from eyes with a uveal melanoma to obtain molecular tumour information.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>DNA was isolated from 65 vitreous fluid samples from enucleated eyes with a uveal melanoma and studied using digital PCR. Primary and additional driver mutations (in <jats:italic>GNAQ<\/jats:italic>, <jats:italic>GNA11<\/jats:italic>, <jats:italic>PLCB4<\/jats:italic>, <jats:italic>CYSLTR2<\/jats:italic>, <jats:italic>BAP1<\/jats:italic>, <jats:italic>SF3B1<\/jats:italic> and <jats:italic>EIF1AX<\/jats:italic>) were investigated using accustomed targeted and drop-off assays. The copy numbers of chromosome 3p and 8q were measured using multiplex and single-nucleotide polymorphism-based assays. Our findings were compared to the molecular profile of matched primary tumours and to the clinicopathological tumour characteristics.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Almost all (63\/65) vitreous fluids had measurable levels of DNA, but melanoma-cell derived DNA (containing the primary driver mutation) was detected in 45\/65 samples (median proportion 15.5%, range 0.03-94.4%) and was associated with a larger tumour prominence, but not with any of the molecular tumour subtypes. Among the vitreous fluids with melanoma-cell derived DNA, not all samples harboured (analysable) other mutations or had sufficient statistical power to measure copy numbers. Still, additional mutations in <jats:italic>BAP1<\/jats:italic>, <jats:italic>SF3B1<\/jats:italic> and <jats:italic>EIF1AX<\/jats:italic> were detected in 15\/17 samples and chromosome 3p and 8q copy numbers matched the primary tumour in 19\/21 and 18\/20 samples, respectively. Collectively, a clinically-relevant molecular classification of the primary tumour could be inferred from 29\/65 vitreous fluids.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>This proof-of-concept study shows that substantial amounts of DNA could be detected in vitreous fluids from uveal melanoma patients, including melanoma-cell derived DNA in 69% of the samples. Prognostically-relevant genetic alterations of the primary tumour could be identified in 45% of the patients. A follow-up study is needed to evaluate our approach in a prospective clinical context. Additionally, our work highlights improved possibilities to sensitively analyse scarce and heterogeneous tumour biopsies, with potential application in other malignancies.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13046-025-03374-y","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T02:07:46Z","timestamp":1744855666000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Digital PCR-based genetic profiling from vitreous fluid as liquid biopsy for primary uveal melanoma: a proof-of-concept study"],"prefix":"10.1186","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3530-3725","authenticated-orcid":false,"given":"R. 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This study was approved by the LUMC Biobank Committee and Medisch Ethische Toetsingscommissie under numbers B14.003\/SH\/sh and B20.026\/KB\/kb. Following the institutional biobank protocol, all patient information has been anonymised and specific consent to participate in the current study was not required.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Following the institutional biobank protocol, all patient information has been anonymised and consent for publication of the current study was not required.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"124"}}