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<p>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 <i>BAP1</i>-mutant, monosomy 3 clones, compared to extrahepatic metastases. <i>BAP1</i> 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.</p>

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Clonal determinants of organotropism and survival in metastatic uveal melanoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月26日

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  • Bailey S. C. L. Jones,
  • Emma Hammes,
  • Patrick C. Demkowicz,
  • Mitchelle Matesva,
  • Renelle Pointdujour-Lim,
  • John H. Sinard,
  • Antonietta Bacchiocchi,
  • Ruth Halaban,
  • Marcus Bosenberg,
  • Mario Sznol,
  • Harriet M. Kluger,
  • Mathieu F. Bakhoum

摘要

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.