TY  - JOUR
AU  - Barwinski, Nicole
AU  - Lever, Mael
AU  - Rating, Philipp
AU  - Jabbarli, Leyla
AU  - Fiorentzis, Miltiadis
AU  - Bechrakis, Nikolaos E
AU  - Lohmann, Dietmar R
AU  - Zeschnigk, Michael
AU  - Le Guin, Claudia H D
TI  - Presence of tumor DNA in aqueous humor is correlated with high risk uveal melanoma.
JO  - Scientific reports
VL  - 15
IS  - 1
SN  - 2045-2322
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2025-01141
SP  - 19406
PY  - 2025
AB  - Metastatic risk stratification is critical for uveal melanoma (UM) management, as approximately up to half of patients develop metastatic disease. Current prognostication for patients undergoing eye-preserving therapies relies on tumor staging and molecular analysis of tumor tissue obtained through potentially invasive biopsy, which can be challenging. While liquid biopsy using cell-free DNA (cfDNA) has emerged as a less invasive alternative for other cancers, studies have shown limited utility of blood-derived cfDNA 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 the time of diagnosis. In this prospective study, AH and/or VB samples were collected from 96 consecutive UM patients undergoing enucleation, transretinal endoresection or transretinal biopsy. DNA was extracted from the ocular fluids and analyzed for the presence of tumor-derived DNA using deep amplicon sequencing targeting mutations in GNAQ and GNA11. This approach achieved an average read depth of 120,000, enabling highly sensitive detection of tumor-specific variants. Tumor DNA was detected in at least one ocular fluid (AH or VB) in 43 of 88 evaluable patients (49
KW  - Humans
KW  - Uveal Neoplasms: genetics
KW  - Uveal Neoplasms: pathology
KW  - Uveal Neoplasms: diagnosis
KW  - Aqueous Humor: metabolism
KW  - Melanoma: genetics
KW  - Melanoma: pathology
KW  - Melanoma: diagnosis
KW  - Uveal Melanoma
KW  - Male
KW  - Female
KW  - Middle Aged
KW  - Aged
KW  - Prospective Studies
KW  - DNA, Neoplasm: genetics
KW  - DNA, Neoplasm: analysis
KW  - Adult
KW  - Aged, 80 and over
KW  - Biomarkers, Tumor: genetics
KW  - Vitreous Body: metabolism
KW  - Mutation
KW  - GTP-Binding Protein alpha Subunits, Gq-G11: genetics
KW  - Prognosis
KW  - GTP-Binding Protein alpha Subunits
KW  - Uveal melanoma (Other)
KW  - Aqueous humor (Other)
KW  - Biomarkers (Other)
KW  - CfDNA (Other)
KW  - Liquid biopsy (Other)
KW  - Ocular liquids (Other)
KW  - Prognostic testing (Other)
KW  - Vitreous body (Other)
KW  - DNA, Neoplasm (NLM Chemicals)
KW  - Biomarkers, Tumor (NLM Chemicals)
KW  - GNA11 protein, human (NLM Chemicals)
KW  - GNAQ protein, human (NLM Chemicals)
KW  - GTP-Binding Protein alpha Subunits, Gq-G11 (NLM Chemicals)
KW  - GTP-Binding Protein alpha Subunits (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40461505
DO  - DOI:10.1038/s41598-025-03915-7
UR  - https://inrepo02.dkfz.de/record/301761
ER  -