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Oncotarget published "Epigenetic reprogramming and aberrant expression of PRAME are associated with increased metastatic risk in Class 1 and Class 2 uveal melanomas" which reported that In this study, we sought to define a threshold value for positive PRAME expression in a large dataset, identify factors associated with PRAME expression, evaluate the prognostic value of PRAME in Class 2 uveal melanomas, and determine whether PRAME expression is associated with aberrant hypomethylation of the PRAME promoter. Class 1 tumors were more likely to be PRAME-, whereas Class 2 tumors were more likely to be PRAME. In Class 1 tumors, PRAME expression was directly associated with SF3B1 mutations and inversely associated with EIF1AX mutations. PRAME expression was strongly associated with hypomethylation at 12 CpG sites near the PRAME promoter. Analyses were performed on 555 de-identified samples from Castle Biosciences, 123 samples from our center, and 80 samples from the TCGA. PRAME is aberrantly hypomethylated and activated in Class 1 and Class 2 uveal melanomas and is associated with increased metastatic risk in both classes. Dr. J. William Harbour from The University of Miami Miller School of Medicine said, "Uveal melanoma is the most common primary cancer of the eye and the second most common form of melanoma." Tumors with the Class 1 profile have a low metastatic risk, whereas those with the Class 2 profile have a high metastatic risk. While the vast majority of metastatic events in uveal melanoma arise from Class 2 tumors, a small subset of Class 1 tumors also give rise to metastasis. Class 1 tumors with low expression of these genes and very low predicted metastatic risk were called Class "1A," whereas those with high expression and higher predicted metastatic risk were called Class "1B."" In our efforts to further improve the prognostic accuracy of the gene array platform, we conducted a genome wide search for new biomarkers and found that mRNA expression of the cancer-testis antigen Preferentially Expressed Antigen in Melanoma was an accurate biomarker for metastasis in Class 1 tumors.

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