Common Genetic Tests in UM (continued)
2 GENE EXPRESSION PROFILE (GEP) TESTING
Based on a 15-GEP test and the expression of the PRAME gene, tumors are grouped into low-, medium- or high-risk for metastasis. l Class 1/PRAME Negative: low risk l Class 1/PRAME Positive: intermediate risk l Class 2: high risk
HLA Testing
Your doctor may recommend a blood test called HLA typing. HLA status refers to a person’s specific human leukocyte antigen (HLA) type, which helps the immune system recognize cells in the body. In ocular melanoma, HLA status is most often used to determine eligibility for certain immunotherapies and clinical trials, particularly T-cell-based treatments that are designed to work only in people with specific HLA types. HLA status does not affect the diagnosis of ocular melanoma and does not change over time. There is currently one FDA-approved systemic treatment for metastatic uveal melanoma (UM): tebentafusp (Kimmtrak), approved in 2022 for patients who test positive for HLA-A*02:01. Clinical trials exploring additional treatment options are ongoing and remain an important consideration for many patients. Therefore, knowing your mutation status may be helpful.
Speak with your doctor about how long it will take to find out the results and whether or not insurance will cover the cost of the test(s). Speaking with a certified genetic counselor may also be helpful.
Genetic Mutations in UM
often associated with older patient age and high risk for metastasis. The BAP1 mutation is strongly associated with a Class 2 gene expression profile (GEP). SF3B1 SF3B1 mutations (seen in ~10–20% of cases) are often linked with intermediate risk of metastasis. EIF1AX EIF1AX mutations (seen in ~10%) are generally linked with a better prognosis and lower risk of metastasis.
A variety of genetic mutations have been found in UM. The following mutations are thought to “drive” the disease: GNAQ and GNA11 The GNAQ and GNA11 mutations are the most common mutations in uveal melanoma, appearing in more than 80% of all cases. These mutations do not seem to be associated with patient outcomes or risk of metastasis. BAP1 The BAP1 mutation is found in about half of uveal melanoma cases. It is most
WHAT DOES THIS MEAN FOR TREATMENT? Mutation status does not guide standard treatment for primary UM, but in metastatic disease it may qualify certain patients for FDA-approved tebentafusp and help determine clinical trial eligibility or surveillance plans.
Speak with your ocular or medical oncologist about what your mutation status could mean and when your tumor should be tested.
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