Single nucleotide polymorphism array analysis of uveal melanomas reveals that amplification of CNKSR3 is correlated with improved patient survival.
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.
Liverpool Ocular Oncology Research Group, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom. s.l.lake@liv.ac.uk
Sarah L
SL
Lake
Bertil E
BE
Damato
Helen
H
Kalirai
Andrew R
AR
Dodson
Azzam F G
AF
Taktak
Bryony H
BH
Lloyd
Sarah E
SE
Coupland
D000368:Aged; D056915:DNA Copy Number Variations / Q000235:genetics; D004745:Enkephalins / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011498:Protein Precursors / Q000378:metabolism; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors; D014604:Uveal Neoplasms / Q000235:genetics* / Q000473:pathology; D000098943:Uveal Melanoma
C496471:CNKSR3 protein, human; D004745:Enkephalins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011498:Protein Precursors; C029992:proenkephalin; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases