current diagnostic techniques (including imaging and liver function tests) are not able to accurately detect micrometastases until tumor nodules have grown considerably, and likely become resistant to therapy. The lack of accurate prognostic tests to identify which patients are at risk of developing clinically overt metastatic disease has been a significant issue in the management of individual patients with uveal melanoma. Without accurate measures of individual metastatic risk, it is impossible to identify which patients are at high risk for clinical metastasis, which can then lead to either over or under-treatment of any given patient. The DecisionDx-UM test was developed to provide improved individual metastatic risk assessment which allows for more appropriate surveillance and treatment planning. DecisionDx-UM GEP Assay Discovery The gene expression profile measured by DecisionDx-UM was discovered in the laboratory of J. William Harbour at Washington University in St. Louis. The application of microarray analysis to primary untreated uveal melanomas revealed that the tumors clustered into two discreet groups based upon their expression profiles. Filtering of the differentially expressed gene set led to the identification of a set of genes able to discriminate between Class 1 and Class 2 tumors. In subsequent experiments, Dr. Harbour’s group assembled microarray information from a larger subset of uveal melanoma tumor samples, and were able to identify candidate discriminatory genes for further analysis. The genetic expression profiles of those discriminating genes were verified in uveal melanoma tumors using quantitative polymerase chain reaction (qPCR) methods, and predictive modeling was performed to identify an optimum set of genes able to accurately predict metastatic risk and report class assignments. The final assay evaluated 12 discriminating genes and 3 control genes to determine Class 1 (low risk) and Class 2 (high risk) tumors, and was validated in a 609 patient multicenter study that included FNAB and FFPE samples. Prognostic Accuracy The current DecisionDx-UM platform was clinically validated in the COOG study, which included 514 patients with UM treated at 12 ocular oncology centers in the United States between 1998 and 2010. The report provides data showing that DecisionDx-UM has a high technical success rate (>95%). Clinical Technical Success Since the initial offering of DecisionDx-UM in December 2009, more than 800 clinical orders have been received for analysis by Castle Biosciences from over 55 ocular oncology centers across the U.S. Technical success and class determination was achieved for 96.2% of the samples. Most of the failures were