The genetics of uveal melanoma: an emerging framework for targeted therapy

Pigment Cell Melanoma Res. 2012 Mar;25(2):171-81. doi: 10.1111/j.1755-148X.2012.00979.x. Epub 2012 Feb 13.


Uveal melanoma is the second most common form of melanoma and the most common primary intraocular malignancy. Until recently, very little was known about the genetics of this aggressive cancer. Mutations in oncogenes and tumor suppressors that are common in other cancers are conspicuously absent in uveal melanoma. In recent years, however, uveal melanoma has begun to yield its secrets, and a fascinating picture is emerging of how it develops and progresses. Mutations in the G(q) alpha subunits, encoded by GNAQ and GNA11, appear to be early or perhaps initiating events that require further mutations for malignant transformation. On the other hand, mutations in the BRCA1-associated protein-1 (BAP1) appear to occur later and demarcate a molecular brink beyond which metastasis becomes highly likely. BAP1 mutations can also occur in the germline, leading to a distinctive cancer predisposition syndrome. These mutations appear to be key events that provide the potential for targeted therapy. This article will review the genetic findings in uveal melanoma over the past two decades and suggest important areas for future work.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chromosome Aberrations
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease
  • Humans
  • Melanoma / epidemiology
  • Melanoma / genetics*
  • Melanoma / pathology
  • Melanoma / therapy*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Molecular Targeted Therapy*
  • Uveal Neoplasms / epidemiology
  • Uveal Neoplasms / genetics*
  • Uveal Neoplasms / pathology
  • Uveal Neoplasms / therapy*


  • MicroRNAs

Supplementary concepts

  • Uveal melanoma