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@ARTICLE{Barwinski:301761,
      author       = {N. Barwinski$^*$ and M. Lever and P. Rating and L. Jabbarli
                      and M. Fiorentzis and N. E. Bechrakis and D. R. Lohmann and
                      M. Zeschnigk and C. H. D. Le Guin},
      title        = {{P}resence of tumor {DNA} in aqueous humor is correlated
                      with high risk uveal melanoma.},
      journal      = {Scientific reports},
      volume       = {15},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2025-01141},
      pages        = {19406},
      year         = {2025},
      abstract     = {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
                      $(49\%),$ with variant allele fractions (VAFs) ranging from
                      0.3 to $50\%.$ Of these positive cases, tumor DNA was
                      identified in VB only in 22 patients, AH only in 5 patients,
                      and both fluids in 16 patients. Importantly, tumor DNA in AH
                      was almost exclusively observed in patients with monosomy 3
                      UM. No significant correlation was found between the
                      presence of tumor DNA in either ocular fluid and primary
                      tumor size or location. Liquid biopsy of AH and VB offers a
                      promising, minimally invasive strategy for obtaining tumor
                      DNA in nearly half of UM patients at diagnosis. The strong
                      association between detectable tumor DNA in AH and monosomy
                      3 status warrants further investigation and may offer
                      valuable insights into UM biology and dissemination
                      mechanisms. This approach may improve risk stratification
                      and inform personalized treatment strategies for patients
                      with UM.},
      keywords     = {Humans / Uveal Neoplasms: genetics / Uveal Neoplasms:
                      pathology / Uveal Neoplasms: diagnosis / Aqueous Humor:
                      metabolism / Melanoma: genetics / Melanoma: pathology /
                      Melanoma: diagnosis / Uveal Melanoma / Male / Female /
                      Middle Aged / Aged / Prospective Studies / DNA, Neoplasm:
                      genetics / DNA, Neoplasm: analysis / Adult / Aged, 80 and
                      over / Biomarkers, Tumor: genetics / Vitreous Body:
                      metabolism / Mutation / GTP-Binding Protein alpha Subunits,
                      Gq-G11: genetics / Prognosis / GTP-Binding Protein alpha
                      Subunits / Uveal melanoma (Other) / Aqueous humor (Other) /
                      Biomarkers (Other) / CfDNA (Other) / Liquid biopsy (Other) /
                      Ocular liquids (Other) / Prognostic testing (Other) /
                      Vitreous body (Other) / DNA, Neoplasm (NLM Chemicals) /
                      Biomarkers, Tumor (NLM Chemicals) / GNA11 protein, human
                      (NLM Chemicals) / GNAQ protein, human (NLM Chemicals) /
                      GTP-Binding Protein alpha Subunits, Gq-G11 (NLM Chemicals) /
                      GTP-Binding Protein alpha Subunits (NLM Chemicals)},
      cin          = {ED01},
      ddc          = {600},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40461505},
      doi          = {10.1038/s41598-025-03915-7},
      url          = {https://inrepo02.dkfz.de/record/301761},
}