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Nearly all eye melanomas start with a mutation in GNAQ or GNA11, which is why skin-melanoma drugs do not work on them; what decides whether the tumour will spread to the liver is a second layer: loss of chromosome 3 with BAP1 mutation and a class 2 gene-expression profile mean high risk, while EIF1AX or SF3B1 mutations and class 1 mean low or delayed risk.
What is measured: the driver and the metastatic risk of a uveal melanoma. How: fine-needle aspiration at the time of plaque brachytherapy or tissue from the enucleated eye, tested for GNAQ or GNA11 (about 90 percent; PLCB4 and CYSLTR2 in most of the rest; BRAF is absent), chromosome 3 and 8q status by FISH, MLPA or SNP array, a 15-gene expression profile (DecisionDx-UM class 1A, 1B or 2, with PRAME status adding risk), BAP1 immunohistochemistry or sequencing, and SF3B1 (late metastases) and EIF1AX (good outlook) mutations; AJCC size, ciliary body involvement and extraocular extension are combined in tools such as the Liverpool Uveal Melanoma Prognosticator Online. What a result changes: class 2 or monosomy 3 with 8q gain carries about a 70 percent risk of metastasis at five years against under 5 percent for class 1A, so it sets surveillance (liver MRI or ultrasound every six months for high risk) and eligibility for adjuvant trials (sunitinib, crizotinib, adjuvant tebentafusp in ATOM); HLA-A*02:01 typing decides tebentafusp in metastatic disease, the only drug with a survival benefit; MEK inhibitors and checkpoint inhibitors have low activity; PRAME-directed T-cell therapies (brenetafusp, IMA203) are in trials. Where it matters: uveal melanoma.
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
Shares HLA-A*02:01 restriction, Brenetafusp, PRAME, Tebentafusp.
Shares HLA-A*02:01 (HLA typing for TCR therapies), Brenetafusp, PRAME, Tebentafusp.
Shares Brenetafusp, PRAME, Tebentafusp, Uveal melanoma.
Shares Brenetafusp, Tebentafusp.
Shares Brenetafusp, PRAME.
Shares Tebentafusp, Uveal melanoma.
Shares HLA-A*02:01 restriction, FISH / ISH (in situ hybridisation).
Shares Tebentafusp, Uveal melanoma.