Single nucleotide polymorphism array analysis of uveal melanomas reveals that amplification of CNKSR3 is correlated with improved patient survival

Am J Pathol. 2013 Mar;182(3):678-87. doi: 10.1016/j.ajpath.2012.11.036. Epub 2013 Jan 26.


Metastatic death from uveal melanoma occurs almost exclusively with tumors showing monosomy of chromosome 3. However, approximately 5% of patients with a disomy 3 uveal melanoma develop metastases, and a further 5% of monosomy 3 uveal melanoma patients exhibit disease-free survival for >5 years. In the present study, whole-genome microarrays were used to interrogate four clinically well-defined subgroups of uveal melanoma: i) disomy 3 uveal melanoma with long-term survival; ii) metastasizing monosomy 3 uveal melanoma; iii) metastasizing disomy 3 uveal melanoma; and iv) monosomy 3 uveal melanoma with long-term survival. Cox regression and Kaplan-Meier survival analysis identified that amplification of the CNKSR3 gene (log-rank, P = 0.022) with an associated increase in its protein expression (log-rank, P = 0.011) correlated with longer patient survival. Although little is known about CNKSR3, the correlation of protein expression with increased survival suggests a biological function in uveal melanoma, possibly working to limit metastatic progression of monosomy 3 uveal melanoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • DNA Copy Number Variations / genetics
  • Enkephalins / metabolism
  • Female
  • Gene Amplification*
  • Genes, Neoplasm / genetics
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate*
  • Male
  • Melanoma / genetics*
  • Melanoma / pathology
  • Membrane Proteins / genetics*
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis*
  • Polymorphism, Single Nucleotide / genetics*
  • Protein Precursors / metabolism
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism
  • Time Factors
  • Uveal Neoplasms / genetics*
  • Uveal Neoplasms / pathology


  • CNKSR3 protein, human
  • Enkephalins
  • Membrane Proteins
  • Neoplasm Proteins
  • Protein Precursors
  • proenkephalin
  • RIPK1 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinases

Supplementary concepts

  • Uveal melanoma