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Biomarkers, genomics, proteomics, and gene regulation
Single Nucleotide Polymorphism Array Analysis of Uveal Melanomas Reveals That Amplification of CNKSR3 Is Correlated With Improved Patient Survival

https://doi.org/10.1016/j.ajpath.2012.11.036Get rights and content
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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.

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Supported by Cancer Research UK (A11634 to S.L.L.) and the North West Cancer Research Fund (CR8559 to S.L.L.). S.E.C., B.E.D., and H.K. are funded by the National Commissioning Group of the National Health Service, UK; A.F.G.T., and A.R.D. are funded by the National Health Service, UK; B.H.L. is funded by the Clatterbridge Centre for Oncology.