Summary
Uveal Melanoma (UM) is a rare cancer resulting from the transformation of melanocytes residing in the uveal tract. Integrative analysis has identified four molecular and clinical subsets in UM. To improve our understanding of UM we performed extensive multi-omics characterization comparing pure melanoma populations obtained from two aggressive UM patient-derived xenograft models with normal choroidal melanocytes. Our study addresses for the first time DNA optical mapping, specific histone mark modifications, DNA topology analysis by Hi-C. Gene expression and cytogenetic analyses suggest that genomic instability is a hallmark of UM. Our study also identified a recurrent deletion in the BAP1 promoter which results in the absence of expression of BAP1 which is associated with high risk of metastases in UM patients. Chromatin topology changes are associated with up-regulation of PRAME, a recognized independent prognostic biomarker in UM and potential therapeutic target. Our findings illustrate how multi-omics integrative approaches can improve the understanding of tumorigenesis and reveals two novel mechanisms of gene expression dysregulation in UM.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵Ω Co-senior Authors.
