Abstract

Uveal melanoma is life-threatening aggressive cancer and comes as a most common primary intraocular malignancy in an adult with the 50% lethality rate usually due to results of metastasis specifically in the liver. After detection of metastasis lesions, the median survival of the patients is 5-7 months. Over the years several developments occur for the diagnosis and therapies of primary uveal melanoma tumors, but the death rate remains unchanged due to the absence of proper metastatic markers which detects 2-5 years after ocular treatments and frequent chemotherapy resistance. The overall data suggest that clear identification of metastatic and non-metastatic tumor phenotype is essential and can have the lifesaving impact for the patients. In order to discover metastatic specific signatures, we have used high-resolution whole-genome copy number variation analysis (Oncoscan) on 20 metastatic (met) and 13 non-metastatic (non-met) FFPE tumors. Genome-wide copy number variation analysis showed more than 2500 loss, gain and LOH events in overall 20 metastatic and 13 non-metastatic samples (15 male and 18 female samples). We observed monosomy 3 in 15 out of 33 (15/33) samples (45.5%), chromosome 6q deletions in 16/33 (48.5%) samples, chromosome 6p gains in 18/33 samples and chromosome 8q gains in 24/33 (72.7%) samples. The bioinformatics analysis picked up 271 unique genes with gain in 75% of the metastatic tumors which did not show gain in non-metastatic tumors. Similarly, the analysis picked up 26 unique genes with gains in 84.6 % of the non-metastatic tumors. Additionally, we observed 477 unique genes with 1 copy loss in 70% of the metastatic tumors and 27 unique genes with 1 copy loss in 61% of the non-metastatic tumors. The findings suggest novel targets that were identified could be useful for prognostication and new therapeutic strategies to control metastasis.