Clonal determinants of organotropism and survival in metastatic uveal melanoma
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.
Authors
- Harriet M. Kluger (ORCID: https://orcid.org/0000-0002-4932-9873)
- Mathieu F. Bakhoum (ORCID: https://orcid.org/0000-0001-8989-8205)
- Ruth Halaban
- John H. Sinard (ORCID: https://orcid.org/0000-0001-8739-517X)
- Patrick Demkowicz (ORCID: https://orcid.org/0000-0002-9566-1033)
- Mitchelle Matesva
- Mario Sznol (ORCID: https://orcid.org/0000-0003-4137-9662)
- Antonietta Bacchiocchi
- Renelle Pointdujour-Lim
- Bailey S. C. L. Jones
- Marcus Bosenberg
- Emma Hammes
Institutions
- Yale Cancer Center (US)
- Yale University (US)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2026-01-26
- DOI
- https://doi.org/10.1038/s41698-026-01274-8
- Primary Topic
- Ocular Oncology and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Yale University
- National Institutes of Health