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PRAME expression in uveal melanoma

PRAME: potential role in uveal melanoma

PRAME (preferentially expressed antigen in melanoma) is an antigen gene that is not expressed at appreciable levels in normal adult tissues, but its expression can become aberrantly increased in some types of cancer, including sarcoma, hematological malignancies, breast cancer, and melanoma. While the exact mechanism of PRAME in these cancers is under investigation, PRAME can repress retinoic acid signaling and thus affect proliferation, differentiation, and apoptosis. Once expressed, the PRAME protein can be processed and presented on the surface of cells, thereby serving as a potential target for therapeutic intervention. There are PRAME-directed therapies being tested in clinical trials for multiple cancer types.

PRAME in Class 1 and 2 uveal melanoma tumors

While the risk for Class 1 patients has been shown to be consistently low across multiple studies, a small proportion of Class 1 tumors do metastasize. The Class 1 sub-classification makes use of two genes within the DecisionDx-UM gene set to identify the lowest-risk Class 1 patients (Class 1A) and those that may have a slightly higher risk of metastasis (Class 1B). 

DecisionDx PRAME unchanged class-predicted risk PRAME negative. Potentially elevated class-predicted risk PRAME positive.

More recently, as published in Clinical Cancer Research, Dr. J. William Harbour and colleagues expanded from using just the 15 genes in the DecisionDx-UM assay to sub-classify Class 1 tumors that do and do not metastasize to using whole transcriptomic analysis. Using this approach, PRAME was identified as the most significantly different gene between these Class 1 tumors. A threshold expression level for determining whether a tumor was PRAME positive or negative was determined.

In the second study of PRAME, published in Oncotarget, Dr. Harbour and colleagues used PRAME gene expression data from 678 uveal melanoma tumors from multiple institutions to refine the threshold that determines PRAME positivity/negativity. This threshold has now been validated in 958 uveal melanoma tumors. The study also examined PRAME in Class 2 tumors, correlations of PRAME with chromosomal aberrations, and PRAME association with DNA mutations.


Although the exact clinical implications of PRAME are currently being evaluated in a prospective multicenter trial led by Dr. Harbour, PRAME has the potential to be important for more precise risk assessment and therapeutic options. Castle Biosciences is offering PRAME testing as an optional add-on test to the DecisionDx-UM test. The ordering physician must indicate on the DecisionDx-UM test order form that they want to order DecisionDx-PRAME.

It is important that the interpretation of PRAME only be done in the context of a DecisionDx-PRAME result. A PRAME-positive result may indicate an increase in metastatic risk for a Class 1 uveal melanoma and a shorter time to metastasis for a Class 2 uveal melanoma. Specific risk estimates associated with PRAME positivity have not yet been determined, pending additional clinical validation. If a tumor is negative for PRAME, the prognosis indicated by the DecisionDx-UM Class is not expected to be altered.


PRAME positive (+) sample report


PRAME negative (-) sample report

Ordering DecisionDx-PRAME

DecisionDx-PRAME can be ordered in conjunction with DecisionDx-UM by electing PRAME testing on the DecisionDx-UM order form.

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DecisionDx-PRAME References

  1. Field MG, Decatur CL, Kurtenbach S, et al. PRAME as an independent biomarker for metastasis in uveal melanoma. Clin Cancer Res 2016;22(5):1234-42.

  2. Walter SD, Chao DL, Feuer W, et al. Prognostic implications of tumor diameter in association with gene expression profile for uveal melanoma. JAMA Ophthalmol 2016;134(7):734-40.