Abstract

What is the significance of PRAME in melanoma? To address this question, we first stratified the survival data of 473 melanoma patients from The Cancer Genome Atlas, which generated Kaplan-Meier survival curves stratified by PRAME RNA expression. We found no significant difference in the survival of patients with tumors showing high versus low PRAME expression. To address the genetic, molecular, and biologic significance of PRAME expression, we analyzed an invasive melanoma in which PRAME protein expression was lost in the deep dermal portion of the specimen. Specifically, we used RNA spatial molecular imaging, a rapidly evolving spatial profiling technology that has the potential to disrupt dermatopathology research. With this dataset, we performed differential gene expression analysis, aiming to understand the overall transcriptomic profiles of PRAME(+) and PRAME(-) malignant melanocytes. These results have provided future targets, pathways, and research avenues to pursue using functional and experimental approaches. This project highlights the incompletely understood significance of PRAME in melanoma as well as the promise of spatial profiling to address this and other vexing questions in dermatopathology.