Melanoma
Melanoma was among the first solid tumours where molecular status directly restructured treatment discussion. BRAF status is established early in advanced disease. Acral and mucosal melanomas, more common in some populations, carry a different molecular profile from sun-exposure-related cutaneous melanoma.
Disease categories
Major disease categories
- Cutaneous melanoma
- Acral melanoma
- Mucosal melanoma
- Uveal melanoma
- Melanoma of unknown primary
Molecular
Molecular considerations
BRAF V600 alterations are central in cutaneous melanoma. NRAS and NF1 alterations define further subgroups. KIT alterations are more frequent in acral and mucosal disease. Uveal melanoma is molecularly distinct, with GNAQ and GNA11 alterations and BAP1 status carrying prognostic weight.
Markers commonly discussed in melanoma
- BRAF V600
- NRAS
- NF1
- KIT
- GNAQ / GNA11 (uveal)
- BAP1 (uveal)
- PD-L1
- TMB
- LDH
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
BRAF testing is standard in advanced cutaneous melanoma; broader panels are discussed particularly in acral, mucosal and uveal disease.
Germline
Germline considerations
CDKN2A assessment is considered where there is multiple primary melanoma or a suggestive family history. BAP1 is relevant in uveal melanoma.
Molecular monitoring
ctDNA and liquid biopsy considerations
ctDNA is studied for monitoring in advanced melanoma, and BRAF-specific assays have been examined for tracking response.
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.
In practice
What a review of this disease typically surfaces
The recurring issue is melanoma subtype recorded loosely. Acral and mucosal melanoma carry a different molecular profile from sun-exposure-related cutaneous disease, and BRAF testing alone leaves those groups under-characterised. Uveal melanoma is molecularly distinct again and does not carry BRAF alterations at all, so approaches developed for cutaneous disease do not transfer.
Patterns observed across precision oncology case reviews. Every case differs; these are the questions worth checking, not conclusions about any individual patient.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Has BRAF status been established in advanced disease?
- Is the melanoma subtype documented, given the differing molecular profiles?
- For uveal melanoma, has BAP1 status been discussed?
Resistance
Resistance and recurrence questions
- Has resistance to targeted therapy been characterised molecularly?
- Has re-biopsy been considered at progression?
Trials
Clinical trial considerations
BRAF status and melanoma subtype substantially shape eligibility.
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.