Uveal Melanoma Genetic Testing: Biopsy, Class 1 vs Class 2 and BAP1

Uveal melanoma genetic testing examines the tumor's own genes to estimate how likely it is to spread. The cells usually come from a fine-needle biopsy taken at the time of treatment. The result does not change how the tumor in the eye is treated, but it can change how often you need liver scans, and it may make you eligible for clinical trials.

This page explains how the biopsy is done, what class 1 and class 2 results mean, what findings such as monosomy 3 and BAP1 indicate, and when inherited (germline) testing is advised for you and your family. For an overview of the disease and its treatment, see uveal melanoma.

Why is uveal melanoma genetic testing done?

Two tumors of the same size can behave very differently, largely because of genetic changes that arise inside the tumor. Testing them allows specialists to:

• estimate the risk of metastasis more precisely than size and location alone;
• match the frequency of liver surveillance to that risk, as the NCCN guideline recommends;
• identify people who may be eligible for clinical trials, including trials of treatment given after eye therapy.

It helps to keep three different tests apart:

HLA typing is not a cancer gene test; it is explained on the follow-up and metastasis page.

How is a fine-needle biopsy of the eye done?

A fine-needle aspiration biopsy (FNAB) collects a tiny sample of tumor cells through a very thin needle. Depending on where the tumor lies, the needle passes either through the eye wall directly over the tumor (the transscleral route, used for tumors toward the front of the eye, with 25–27 gauge needles) or through the gel inside the eye (the transvitreal route, with a needle or a small vitrectomy instrument). The biopsy is usually taken during the operation to place a radiation plaque, or shortly before radiation.

It has two possible purposes: to confirm the diagnosis when a lesion is atypical — for example a non-pigmented tumor or a suspected metastasis — and, more often today, to provide cells for prognostic testing. Other diagnostic tests are described on how eye tumors are diagnosed.

Diagnostic reliability is reported at 88–95%, with false-negative results in about 3–7%. Possible complications include temporary bleeding inside the eye, bleeding under the retina and retinal detachment; seeding of tumor cells along the needle track is rare and less likely with needles of 25 gauge or finer. The biopsy does not affect how well the tumor responds to its treatment.

1. Discussion. You and your ocular oncologist consider whether the result would change your follow-up or open access to a trial.
2. Sampling. The biopsy is taken, most often during plaque surgery or just before radiation.
3. Laboratory analysis. The cells are examined under the microscope and tested for gene activity or chromosome changes.
4. Results consultation. The findings are explained together with the tumor's size and location.
5. A personal follow-up plan. Liver surveillance is scheduled according to your risk group, in coordination with medical oncology.

What do class 1A, 1B and 2 mean?

A commercially available gene expression profile (GEP) test, DecisionDx-UM, measures the activity of 12 genes (plus 3 control genes) and sorts tumors into classes. It was validated in a prospective study of 514 patients at 12 centers, and it produces a result in more than 95% of samples.

A second marker, PRAME, adds another layer. PRAME is a gene that is switched on in some tumors, and its expression raises the risk within each class. In the original research, none of the PRAME-negative class 1 tumors spread, while all seven class 1 tumors that did spread were PRAME-positive; the test threshold was later confirmed in 958 tumors. Reported 5-year metastasis-free survival is about 81% for class 1 PRAME-positive tumors and about 45% for class 2 PRAME-positive tumors.

What do chromosome 3 and 8q results mean?

Some centers analyze the tumor's chromosomes rather than its gene activity. Uveal melanoma cells often gain or lose whole sections of chromosomes, and the key findings are:

• monosomy 3 — loss of one of the two copies of chromosome 3, the strongest single marker of high risk;
• gain of 8q — extra copies of the long arm of chromosome 8, which adds to the risk, especially together with monosomy 3, and more so the more copies are present;
• gain of 6p — linked with a more favorable outlook in tumors that keep both copies of chromosome 3;
• loss of 1p — an additional unfavorable finding.

What are BAP1, SF3B1 and EIF1AX?

Most uveal melanomas begin with a change in the GNAQ or GNA11 gene (about 90% of tumors at the back of the eye) or, less often, in CYSLTR2 or PLCB4. These starting changes do not predict behavior; a second change, usually in one of three genes that rarely occur together, does:

A BAP1 change found in the tumor is not the same as an inherited BAP1 change. In most patients, the tumor's BAP1 change arose only in the tumor cells and cannot be passed on to children.

Is uveal melanoma inherited? BAP1 tumor predisposition syndrome

Uveal melanoma is usually not inherited. However, about 1–2% of all patients — and 20–30% of patients from families with more than one case — carry an inherited (germline) BAP1 change, a condition called BAP1 tumor predisposition syndrome. Carriers tend to develop uveal melanoma at a younger age (a mean of 50.5 years versus 62), and they have a higher risk of certain other tumors: mesothelioma, skin melanoma, kidney cancer, basal cell carcinoma, meningioma, cholangiocarcinoma and particular skin growths called BAP1-inactivated melanocytic tumors. Each child of a carrier has a 50% chance of inheriting the change.

Germline testing, with genetic counseling before and after, is worth discussing if:

• you have had two or more BAP1-related tumors, or one such tumor and a first- or second-degree relative with one;
• you were diagnosed young, or have tumors in both eyes or several tumors in one eye;
• relatives have had uveal melanoma, mesothelioma, kidney cancer or skin melanoma.

For carriers, published recommendations include a yearly dilated eye examination starting between about 11 and 18 years of age, a yearly full skin examination from about 18, and, from about 30, kidney imaging every two years (alternating ultrasound and MRI) together with a yearly examination.

How do the results change follow-up?

The most practical use of genetic results is to set the intensity of surveillance. Features that place a patient in a higher-risk group include large tumor size, ciliary body involvement, epithelioid cells, monosomy 3 or 8q gain, a class 2 profile, BAP1 loss and PRAME expression. Under the 2026 NCCN guideline, liver imaging then ranges from once a year for low-risk patients to every 3–6 months for high-risk patients, for up to 10 years.

High-risk results can also open access to trials of treatment after eye therapy. As of September 2026, two phase 3 trials are testing this: ATOM, which gives tebentafusp to high-risk patients who are HLA-A*02:01-positive, and OptimUM-11, which tests darovasertib plus crizotinib regardless of tissue type. Both are investigational; no treatment has yet been proven to prevent metastasis.

Results can be emotionally difficult. A high-risk result does not mean the melanoma will certainly spread, and a low-risk result does not mean follow-up can stop. Prof. Türkoğlu explains results in the context of the tumor's size and location and coordinates surveillance with medical oncology; see also prognosis and survival.