The genetic evolution of metastatic uveal melanoma.
A Hunter ShainMette M BaggerRichard YuDarwin ChangShanshan LiuSwapna VemulaJingly F WeierKarin A W WadtSteffen HeegaardBoris C BastianJens Folke KiilgaardPublished in: Nature genetics (2019)
Uveal melanoma is a clinically distinct and particularly lethal subtype of melanoma originating from melanocytes in the eye. Here, we performed multi-region DNA sequencing of primary uveal melanomas and their matched metastases from 35 patients. We observed previously unknown driver mutations and established the order in which these and known driver mutations undergo selection. Metastases had genomic alterations distinct from their primary tumors; metastatic dissemination sometimes occurred early during the development of the primary tumor. Our study offers new insights into the genetics and evolution of this melanoma subtype, providing potential biomarkers for progression and therapy.
Keyphrases
- skin cancer
- squamous cell carcinoma
- small cell lung cancer
- end stage renal disease
- ejection fraction
- chronic kidney disease
- copy number
- prognostic factors
- basal cell carcinoma
- single cell
- gene expression
- stem cells
- circulating tumor
- single molecule
- dna methylation
- mesenchymal stem cells
- bone marrow
- smoking cessation