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I.W. McLean, A.E. Director-Myska, R.L. Becker, J.S. White; Comparative Genomic Hybridization of Uveal Malignant Melanoma . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1549.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To study the genomic changes in uveal melanoma characterized by gains or loses of minor chromosomal bands that are associated with metastasis of the tumor. Methods: Comparative genomic hybridization (CGH) was utilized to elucidate DNA sequence copy number imbalances in 100 archival formalin-fixed paraffin-embedded (FFPE) uveal melanoma cases. Of these 100 cases, 51 were from patients who survived 9 years or more post-diagnosis without evidence of metastasis, and the remaining 49 patients died from metastatic disease. A viable probe was generated from 82 of the 100 cases, allowing correlation of CGH findings with survival for all but 18 of the cases. Copy number imbalances observed in CGH were tested for univariate prognostic significance. Results: There were five chromosomal minor bands in which gains were associated significantly with metastatic death. These were in order of decreasing significance: 18q11.2, 6q16, 21q11.2, 9q12, and 3q12. There was a single region where a loss was associated with patient outcome. This was 1p33. Overall, the strongest correlation with prognosis was associated with a gain of 18q11.2 (p = 0.0037). Gain of 18q11.2 and concomitant loss of 1p33 was the strongest multivariate predictor of prognosis (p = 0.0028) Conclusion: This large-scale CGH analysis of archival material is intended to direct further gene-specific study of malignancy in uveal melanoma. This study has to be interpreted with a note of caution. Comparative Genomic Hybridization provides the average genome of all of the cells sampled. We believe that there is marked heterogeneity in the population of tumor cells in uveal melanoma. We should be looking at the genome of the most malignant cells not the average cell, if we want to find the genes associated with metastasis. This could be the reason why we failed to find a significant association with losses of genetic material in chromosome 3 and prognosis.
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