Contribution of CDKN2A/P16 ( INK4A ), P14 (ARF), CDK4 and BRCA1/2 germline mutations in individuals with suspected genetic predisposition to uveal melanoma

Fam Cancer. 2010 Dec;9(4):663-7. doi: 10.1007/s10689-010-9379-9.


Uveal melanoma arises from melanocytes of the uveal tract (iris, ciliary body and choroid) and represents the most common intraocular malignancy in adults. Some rare clinical situations (young age at diagnosis, bilateral or multifocal forms, association with cutaneous malignant melanoma and/or familial aggregations of melanomas) are suggestive of genetic susceptibility. The aim of this study was to evaluate the contribution of CDKN2A/P16INK4A, P14ARF and CDK4 gene germline mutations in a series of patients with uveal melanoma recruited in a single institution with a clinical presentation indicative of genetic predisposition. Molecular analyses were proposed to 36 patients and were performed in 25 cases. The contribution of BRCA1/2 gene germline mutations in patients with uveal melanoma and a personal and/or family history of breast/ovarian cancers was also evaluated. Molecular analysis of BRCA1/2 genes was proposed to 35 patients and was performed in 25 patients. No deleterious germline mutation was identified in either group of patients. These results indicate that the CDKN2A/P16INK4A, P14ARF, CDK4 genes are not responsible for the vast majority of genetic susceptibility to uveal melanoma. They also suggest that one case of uveal melanoma in a family with a history of breast cancer is not sufficient to justify BRCA1/2 genetic testing when the classical criteria for molecular analysis are not present. International studies are ongoing in melanoma-prone families in an attempt to identify uveal melanoma susceptibility loci and genes.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cyclin-Dependent Kinase 4 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • DNA, Neoplasm / genetics
  • Female
  • Genetic Predisposition to Disease*
  • Genetic Testing
  • Germ-Line Mutation / genetics*
  • Humans
  • Male
  • Melanoma / genetics*
  • Melanoma / pathology
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Pedigree
  • Polymerase Chain Reaction
  • Prognosis
  • Tumor Suppressor Protein p14ARF / genetics*
  • Uveal Neoplasms / genetics*
  • Uveal Neoplasms / pathology
  • Young Adult


  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Neoplasm
  • Tumor Suppressor Protein p14ARF
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4