Uveal Melanoma
Uveal melanoma arises in the eye and is molecularly distinct from cutaneous melanoma. It does not carry BRAF alterations, and treatment approaches developed for skin melanoma do not transfer to it.
Disease categories
Major disease categories
- Choroidal melanoma
- Ciliary body melanoma
- Iris melanoma
- Metastatic uveal melanoma
Molecular
Molecular considerations
GNAQ and GNA11 alterations are near-universal and definitional. BAP1 loss, SF3B1 and EIF1AX alterations define prognostic groups, with BAP1 loss associated with substantially higher metastatic risk. Monosomy 3 is a long-established prognostic marker.
Markers commonly discussed in uveal melanoma
- GNAQ / GNA11
- BAP1
- SF3B1
- EIF1AX
- Monosomy 3
- HLA-A*02:01 status
Not exhaustive, and not every marker is assessed in every patient. Which of these is relevant depends on the individual case and should be discussed with the treating team.
Testing
Genomic testing considerations
Prognostic molecular classification on the primary tumour is widely discussed, because it determines surveillance intensity.
Germline
Germline considerations
Germline BAP1 assessment is discussed, as BAP1 tumour predisposition syndrome carries implications for relatives and for other tumour types.
Molecular monitoring
ctDNA and liquid biopsy considerations
An area of research interest, particularly for detecting liver metastasis early.
Single-cell & computation
Single-cell and algorithmic approaches
Single-cell sequencing in skin malignancy is used to characterise immune infiltration and exhaustion states, which bear directly on how these tumours behave. Single-cell DNA analysis resolves clonal structure in tumours with very high mutational burden, where bulk calls can be difficult to attribute. Algorithm work includes mutational signature deconvolution, neoantigen prediction pipelines, and models of resistance emergence under targeted therapy.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Has prognostic molecular testing been performed on the primary tumour?
- Is liver surveillance in place, given the characteristic metastatic pattern?
- Has germline BAP1 testing been discussed?
Resistance
Resistance and recurrence questions
- Has the metastatic pattern been reassessed?
Trials
Clinical trial considerations
Uveal melanoma trials are separate from cutaneous melanoma trials; HLA type affects eligibility for some.
When a precision oncology review may help
A review is most useful where the standard pathway has been exhausted or where the picture is more complicated than a protocol accounts for — rare presentations, treatment resistance, complex or apparently contradictory molecular findings, or a decision between several defensible options.
The output is a structured analysis and a set of questions for the treating team. It is not treatment, and it does not replace the treating oncologist.