BAP1 deficiency causes loss of melanocytic cell identity in uveal melanoma

Katie A. Matatall, Olga A. Agapova, Michael D. Onken, Lori A. Worley, Anne M. Bowcock, J. W. Harbour

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113 Scopus citations


Background: Uveal melanoma is a highly aggressive cancer with a strong propensity for metastasis, yet little is known about the biological mechanisms underlying this metastatic potential. We recently showed that most metastasizing uveal melanomas, which exhibit a class 2 gene expression profile, contain inactivating mutations in the tumor suppressor BAP1. The aim of this study was to investigate the role of BAP1 in uveal melanoma progression.Methods: Uveal melanoma cells were studied following RNAi-mediated depletion of BAP1 using proliferation, BrdU incorporation, flow cytometry, migration, invasion, differentiation and clonogenic assays, as well as in vivo tumorigenicity experiments in NOD-SCID-Gamma mice.Results: Depletion of BAP1 in uveal melanoma cells resulted in a loss of differentiation and gain of stem-like properties, including expression of stem cell markers, increased capacity for self-replication, and enhanced ability to grow in stem cell conditions. BAP1 depletion did not result in increased proliferation, migration, invasion or tumorigenicity.Conclusions: BAP1 appears to function in the uveal melanocyte lineage primarily as a regulator of differentiation, with cells deficient for BAP1 exhibiting stem-like qualities. It will be important to elucidate how this effect of BAP1 loss promotes metastasis and how to reverse this effect therapeutically.

Original languageEnglish
Article number371
JournalBMC Cancer
StatePublished - 5 Aug 2013
Externally publishedYes


  • BAP1
  • Differentiation
  • Metastasis
  • Stem cell
  • Tumor suppressor
  • Uveal melanoma


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