Molecular Analysis of Uveal Melanoma

      Onken et al
      • Onken M.D.
      • Worley L.A.
      • Char D.H.
      • et al.
      Collaborative Ocular Oncology Group Report Number 1: Prospective Validation of a Multi-Gene Prognostic Assay in Uveal Melanoma.
      report a prospective evaluation of a gene expression profiling (GEP)-based assay, designed around 15 genes, that assigns uveal melanoma (UM) to 2 prognostic subgroups: Classes 1 and 2, which respectively are associated with low and high risks of metastasis. In 260 UM patients, they compared GEP with detection of chromosome 3 loss of heterozygosity using a single nucleotide polymorphism (SNP) assay, stating that GEP is better at predicting metastatic risk. They also claim that GEP is more accurate than other cytogenetic- or molecular methods, which they dismiss as ‘not suitable for routine clinical use.' In our opinion, the authors' claims and criticisms are not founded on adequate scientific data.

      References

        • Onken M.D.
        • Worley L.A.
        • Char D.H.
        • et al.
        Collaborative Ocular Oncology Group Report Number 1: Prospective Validation of a Multi-Gene Prognostic Assay in Uveal Melanoma.
        Ophthalmology. 2012; 119: 1596-1603
        • Onken M.D.
        • Worley L.A.
        • Person E.
        • et al.
        Loss of heterozygosity of chromosome 3 detected with single nucleotide polymorphisms is superior to monosomy 3 for predicting metastasis in uveal melanoma.
        Clin Cancer Res. 2007; 13: 2923-2927
        • Damato B.
        • Dopierala J.A.
        • Coupland S.E.
        Genotypic profiling of 452 choroidal melanomas with multiplex ligation-dependent probe amplification.
        Clin Cancer Res. 2010; 16: 6083-6092
        • Lake S.L.
        • Damato B.E.
        • Kalirai H.
        • et al.
        Single nucleotide polymorphism array analysis of uveal melanomas reveals that amplification of CNKSR3 is correlated with improved patient survival.
        Am J Pathol. 2013; 182: 678-687
        • Eleuteri A.
        • Damato B.
        • Coupland S.E.
        • Taktak A.F.G.
        Enhancing survival prognostication in patients with choroidal melanoma by integrating pathologic, clinical and genetic predictors of metastasis.
        IJBET. 2012; 8: 18-35

      Linked Article

      • Collaborative Ocular Oncology Group Report Number 1: Prospective Validation of a Multi-Gene Prognostic Assay in Uveal Melanoma
        OphthalmologyVol. 119Issue 8
        • In Brief
          This study evaluates the prognostic performance of a 15 gene expression profiling (GEP) assay that assigns primary posterior uveal melanomas to prognostic subgroups: class 1 (low metastatic risk) and class 2 (high metastatic risk).
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      • Author reply
        OphthalmologyVol. 120Issue 7
        • In Brief
          We appreciate the opportunity to respond to the letter by Coupland and Damato regarding our 2012 article.1 Contrary to their claim, the gene expression profile (GEP) prognostic test for uveal melanoma has undergone much greater validation than any other competing technology, and it is the only one that has been validated in a prospective multicenter study. It meets the highest National Comprehensive Cancer Network “level I” evidence for cancer biomarkers, whereas the Liverpool group has achieved only a level III with their multiplex ligation-dependent probe amplification (MLPA) technique.
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