Multiregional genetic evolution of metastatic uveal melanoma

Daniel A. Rodriguez, Jessica Yang, Michael A. Durante, Alexander N. Shoushtari, Stergios J. Moschos, Kazimierz O. Wrzeszczynski, J. William Harbour, Richard D. Carvajal

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and leads to deadly metastases for which there is no approved treatment. Genetic events driving early tumor development are well-described, but those occurring later during metastatic progression remain poorly understood. We performed multiregional genomic sequencing on 22 tumors collected from two patients with widely metastatic UM who underwent rapid autopsy. We observed multiple seeding events from the primary tumors, metastasis-to-metastasis seeding, polyclonal seeding, and late driver variants in ATM, KRAS, and other genes previously unreported in UM. These findings reveal previously unrecognized temporal and anatomic complexity in the genetic evolution of metastatic uveal melanoma, and they highlight the distinction between early and late phases of UM genetic evolution with implications for novel therapeutic approaches.

Original languageEnglish (US)
Article number70
Journalnpj Genomic Medicine
Issue number1
StatePublished - Dec 2021
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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