Genetic aspects of uveal melanoma: a brief review

Semin Oncol. 1996 Dec;23(6):768-72.


Uveal melanoma usually occurs sporadically in the absence of obvious genetic predisposing factors. However, in rare patients, there is a suggestion that there may be genetic predisposition. Rare occurrences of familial uveal melanoma are believed to be inherited in an autosomal dominant mode. There are a few clinical conditions that can predispose to or be associated with uveal melanoma, including ocular melanocytosis, neurofibromatosis type I, and familial atypical mole and melanoma syndrome. Nonrandom cytogenetic changes in uveal melanoma are characterized by monosomy 3, trisomy 8, and structural or numerical abnormalities of chromosome 6. Alterations of chromosome 9p are less frequently observed. CDKN2 gene, a cutaneous melanoma predisposition gene, is probably not a uveal melanoma predisposition gene as evidenced by the lack of somatic mutations involving this gene in uveal melanoma samples and the absence of germline mutations in familial uveal melanoma patients. Transgenic mouse models developed using a tyrosinase promoter tagged with a mutated ras gene or SV40-Tag oncoprotein develop retinal pigment epithelium tumors that resemble uveal melanoma. We propose that uveal melanoma cases be categorized on genetic basis according to a new classification system. This classification scheme will help to identify and uniformly categorize uveal melanoma patients with genetic predisposition. Such patients offer unique opportunities for studying the genetic aspects of uveal melanoma and, therefore, appropriate tissue samples should be obtained from them for molecular genetic studies. Further studies are needed to fully understand the genetic aspects of uveal melanoma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Cyclin-Dependent Kinases / biosynthesis
  • Cyclin-Dependent Kinases / genetics
  • Dysplastic Nevus Syndrome / genetics
  • Enzyme Inhibitors
  • Genes, Dominant
  • Genes, p53
  • Genes, ras
  • Germ-Line Mutation
  • Humans
  • Li-Fraumeni Syndrome / genetics
  • Melanoma / classification
  • Melanoma / genetics*
  • Mice
  • Mice, Transgenic
  • Neurofibromatosis 1 / genetics
  • Nevus of Ota / genetics
  • Pedigree
  • Proto-Oncogene Proteins*
  • Terminology as Topic
  • Uveal Neoplasms / classification
  • Uveal Neoplasms / genetics*


  • Enzyme Inhibitors
  • Proto-Oncogene Proteins
  • CDK4 protein, human
  • Cdk4 protein, mouse
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases