Abstract
Uveal melanoma (UM), the most common intraocular cancer in adults, metastasizes to the liver in 90% of cases. Integrating DNA sequencing of 144 metastases with decade-long patient outcomes, we found that liver metastases are more enriched for BAP1-mutant, monosomy 3 clones, compared to extrahepatic metastases. BAP1 loss in liver metastases independently predicts poorer post-metastatic survival. Patterns of dissemination are set early in primary tumors, enabling molecular profiling to forecast metastatic spread.
Data availability
Clinical data is available upon request. All patients’ data analyzed from published studies are publicly available accordingly. All raw sequencing data generated for this study will be deposited to NCBI’s Gene Expression Omnibus (GEO) database prior to publication. The Ny et al. 2021 data is available in the European Genome-phenome Archive (EGA) under the accession code EGAS00001005478. The Karlsson et al. 2020 data used in this study is available in EGA under the accession code EGAS00001004296. The Nguyen et al.11 data was download from the cBioPortal study MSK-MetTropism (MSK, Cell 2021) and was filtered for patients with metastatic uveal melanoma. The TCGA Uveal melanoma data by Robertson et al.9 was accessed through cBioPortal (Uveal Melanoma (TCGA, PanCancer Atlas))18,19,20,21,22,23,24,25.
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Acknowledgements
We would like to acknowledge the Specimen Resource Core Yale SPORE in Skin Cancer for their samples and analysis provided for this study. M.F.B. is supported by NIH Research Grant P30CA016359 and 2P50CA121974 from the National Cancer Institute, R21EY035090 from the National Eye Institute, by the Office of the Assistant Secretary of Defense for Health Affairs through the Melanoma Research Program under Award No. HT9425-23-1-1070, and by a grant from the Connecticut Lions Eye Research Foundation.
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B.J. and M.F.B. designed the study. B.J., E.H., P.D., M.M., R.L., J.S., M.B., M.S., and H.K. collected and/or reviewed clinical data. A.B. and R.H. supplied tumor specimens and performed sequencing. M.F.B. supervised the project, and, together with B.J., drafted the manuscript with input from all authors.
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Jones, B.S.C.L., Hammes, E., Demkowicz, P.C. et al. Clonal determinants of organotropism and survival in metastatic uveal melanoma. npj Precis. Onc. (2026). https://doi.org/10.1038/s41698-026-01274-8
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DOI: https://doi.org/10.1038/s41698-026-01274-8
