In the United States, uveal melanoma (UM) accounts for 85% of ocular melanoma and 5% of all melanomas. This translates to approximately 1,500 new cases each year.

Even with optimal treatment, the risk of metastasis with this condition is high (up to 50%) and occurs, on average, three years following treatment of the primary ocular melanoma 1. Early and accurate diagnosis is critical for the management of this malignancy.

The standard of care for diagnosing UM involves direct biopsy of tumors originating in the uveal tract.

Identifying tumor biomarkers early may improve the chances of early detection of primary and metastatic lesions — and may potentially accelerate the treatment process significantly.

Findings suggest effective liquid biopsy for uveal melanoma

Researchers at the USC Roski Eye Institute, part of Keck Medicine of USC, are conducting studies exploring the potential of aqueous humor (AH) liquid biopsy to serve as an adjunct and possibly an alternative to the standard tumor biopsy.

“Liquid biopsy is evolving, and Keck Medicine is evaluating aqueous humor liquid biopsy as an alternative to direct tumor biopsy, which has some risks,” said Jesse Lee Berry, MD, director of ocular oncology at the USC Roski Eye Institute. “This is allowing for molecular diagnosis, prognostication and maybe more.”

Berry and several colleagues recently published a study in the International Journal of Molecular Science outlining the diagnostic, “Potential of Aqueous Humor as a Liquid Biopsy for Uveal Melanoma 2.”

In the study, AH liquid samples were taken before or after radiation from 12 choroidal and eight ciliary body (CB) melanoma eyes.

Samples were analyzed for nucleic acid concentrations, genomic sequencing and Illumina sequencing to detect somatic copy number alterations (SCNAs).

Berry and her team observed that AH is a source of circulating tumor DNA (ctDNA) in the eyes of patients with uveal melanoma.

Additionally, for the first time, they identified uveal melanoma SCNAs and mutations in AH-derived ctDNA.

Concordance was particularly strong between SCNAs from primary tumors and matched post-radiation AH in ciliary body melanoma eyes.

These promising findings suggest that AH can serve as an effective liquid biopsy for uveal melanoma.

Potential implementation of aqueous humor liquid biopsy

Berry and her team are still studying the applications of AH liquid biopsy, but they are confident that its incorporation into standard practice is soon to be actualized.

“I suspect in the next five years AH liquid biopsy will be done in addition to [tumor biopsy],” Berry said. “In small tumors, [it] may be used instead of tumor biopsy.

“With further investigations, this novel AH liquid biopsy platform may allow clinicians to better prognosticate, monitor disease progression and investigate local intraocular biomarkers for uveal melanoma.”