• Ocular Pathology/Oncology

    Review of: Potential of aqueous humor as a liquid biopsy for uveal melanoma

    Im D, Peng C, Xu L, et al. International Journal of Molecular Sciences, June 2022

    The validation of aqueous humor (AH) for liquid biopsies has the potential to improve accessibility and the relative safety of sample collection for genetic analysis of ocular tumors. In this study, researchers examined the difference between circulating tumor DNA (ctDNA) from AH of eyes with uveal melanoma that underwent radiation treatment prior to collection and those that did not.

    Study design

    This is a single-center pilot study that aimed to investigate whether ctDNA could be isolated from AH and serve as a surrogate for tumor biopsy in uveal melanoma (UM). The study evaluated 37 AH samples (obtained before or after tumor radiation) and 1 tumor wash sample from 20 eyes with UM, including 12 choroidal and 8 ciliary body (CB) tumors. AH samples were analyzed for nucleic acid concentration. Both AH DNA and the tumor wash sample underwent shallow whole-genome sequencing followed by Illumina sequencing to detect somatic copy number alterations (SCNAs). Four AH samples (following radiation) underwent targeted sequencing of the BAP1 and GNAQ genes.

    Outcomes

    The AH samples that were analyzed following radiation had significantly higher concentrations of detectable DNA and miRNA compared to samples obtained prior to radiation. AH from ciliary body UM was more likely to yield detectable SCNAs, which were identified in 6/8 post-radiation CB UM compared to 0/11 post-radiation choroidal UM. SCNAs in AH from post-radiation CB were highly concordant with its matched tumor. BAP1 or GNAQ variants were detected in 3/4 of post-radiation AH samples.

    Limitations

    This is a pilot study with a small number of samples. The impact of radiation on ctDNA alternation is unknown. It is encouraging that ctDNA in eyes with UM, particularly CB tumors, can potentially be collected from AH. Further investigation is warranted.

    Clinical significance

    This is the first study to show that SCNAs can be identified from AH-derived ctDNA in UM eyes, particularly eyes with ciliary body UM. Detectable levels were much higher following radiation. The study results provide optimism that AH could potentially serve as a site for liquid biopsy for UM.