Circulating tumor DNA is found in the aqueous humor of eyes with uveal melanoma

In eyes with uveal melanoma, measurable amounts of tumor DNA were found in the aqueous humor, suggesting that this liquid medium could provide a minimally invasive biopsy option for uveal melanoma prognostication.

Study design

This was a case series study at a tertiary eye center that included 37 aqueous humor samples from 20 eyes of 20 patients with uveal melanoma (12 choroidal melanomas and 8 ciliary body melanomas). Aqueous humor samples included paired pre-radiation (at plaque placement) and post-radiation (at plaque removal) samples from 17 eyes (9 choroidal melanomas and 8 ciliary body melanomas); an additional 2 samples were post-radiation only, and 1 sample was from after enucleation without radiation. Samples underwent shallow whole-genome sequencing followed by Illumina sequencing to detect somatic copy number alterations (SCNAs) of the DNA. Additional BAP1- and GNAQ-targeted gene sequencing was performed on 4 post-radiation aqueous humor samples.

Outcomes

Highly recurrent SCNAs were not identified in any of the post-radiation choroidal samples but were found in 6 of 8 post-radiation ciliary body aqueous humor samples. A tumor wash was performed in one case and revealed high concordance in SCNAs between the post-radiation ciliary body and its matched tumor (r = 0.978). Variants of BAP1 or GNAQ were detected in 3 of 4 post-radiation aqueous humor samples.

Limitations

The sample size of this study was small, with only 20 patients with uveal melanoma included. There were no highly recurrent SCNAs in eyes with choroidal melanoma, but the majority of the choroidal tumors studied were relatively small, precluding any conclusions about the effect of choroidal tumor size on the yield of the aqueous humor analysis. Due to potential risks associated with tumor biopsy, the researchers did not perform additional tumor biopsy for research purposes and had to rely on information from Castle Biosciences testing, which was not available for all patients.

Clinical significance

This study shows that aqueous humor obtained from eyes with uveal melanoma, particularly those with post-radiation ciliary body tumors, contains circulating tumor DNA. Due to the relative ease of obtaining sample from the aqueous humor, this technique can have important implications for prognostic testing in patients with uveal melanoma.

Financial Disclosures: Dr. Arman Mashayekhi discloses no financial relationships.