 Hi, I'm here to discuss our article that was recently published in Anka Target this fall Which was titled epigenetic reprogramming and a barrant expression of Prame are associated with increased Metastatic risk in class 1 and class 2 UBio melanomas My name is Matthew Field and I'm an MD PhD candidate at the University of Miami and first author on this paper This work was conducted In Dr. Harbour's laboratory and he's an ocular oncologist at the University of Miami And this was also done in collaboration with Castle biosciences So first just to give a little bit of an introduction on UVa melanoma UVa melanoma is the most common primary tumor of the eye and second most common type of melanoma There's approximately 2,000 cases per year in the United States about 50% of patients that get UVa melanoma develop metastatic disease One of the questions Dr. Harbour asked was whether he could use a molecular assay to Determine which UVa melanomas were at lower or increased risk of metastasis and he found that Using a panel of genes you could delineate Low-risk UVa melanomas from high-risk melanomas the low-risk UVa melanomas were classified as class 1 and the high Metastatic risk UVa melanomas were classified as class 2 This gene expression profile test is used Throughout the United States and many other locations. We have now found recently that though most of the Patients that metastasize are class 2 a small proportion of class 1 patients also metastasized and We previously Published an article showing that these class 1 patients that metastasized had increased mRNA expression in a gene called Prem Preferentially expressed antigen and melanoma since that initial manuscript we then Further evaluated Prem in a much larger cohort of patients and we also looked at Prem expression in both class 1 and class 2 and That was a large part about what this Manuscript an onka target was about as part of this we worked with castle to get Prem expression data in the large cohort of patients in 678 samples we looked at Prem expression 498 were Prem negative and 180 were Prem positive we then looked at both class 1 and class 2's and Prem positivity was Associated with shorter time to metastasis and melanoma specific mortality in both class 1's and class 2's This was very interesting to us Because it allowed us for the first time in class 1's to provide prognostic information for Patients that might metastasize out of the class 1's most class 1 patients do not metastasize But the small percentage that do were very associated with high Prem expression and then in class 2 patients Even though most class 2 patients metastasized if you had Prem positivity They tended to do even worse we looked at 12 different CPG sites within the Prem promoter and all 12 of these CPG sites had hypo methylation in Prem positive tumors compared to the Prem negative tumors So this suggested that the way that Prem became overexpressed or increase in expression was that the promoter region which is typically hyper methylated Became hypo methylated and that allowed Prem to be increased in expression we then looked at Prem expression in many different tissues and Interestingly Prem is really only expressed in the testes The fact that there are almost no tissues that are expressing Prem in the body would suggest that perhaps a Immunotherapeutic trial against Prem would not have that many off-target effects We would love to collaborate and try to initiate a clinical trial or start something where we could give you be a melanoma patients that have Prem Positivity and opportunity to enroll and see if therapeutic targets against Prem might have an effect to take our findings further on Prem We've now established co-op to to both retrospectively and Prospectively assess Prem status in a large cohort of patients co-op to encompasses approximately 30 centers and many different ocular Psychologists and we are going to correlate Prem expression with outcomes in these patients and follow many patients prospectively to see whether Prem is predictive of worse disease and worse outcome so we're very excited about our results and It's an exciting time and potentially We have found a new target that could be used in immunotherapies and also for prognostic purposes So thank you very much and you know, please contact me if you have any questions