Molecular Factors of Tumor Progression in Uveal Melanoma
Materials and methods. There were examined and treated 30 patients (12 males and 18 females, 2:3 ratio) aged 23-72 (average age 52.5 ± 9.1 years) with primary UM. In all cases, patients underwent enucleation with histologically confirmed diagnosis of UM. Mutations in genes GNAQ/GNA11 and polymorphism in gene ABCB1/MDR1 were assessed by using PCR-RFLP analysis. Results. It was found that 27 (90%) out of 30 samples contained mutations in exon 4 and 5 of genes GNAQ/GNA11. Rate of mutations in exon 4 and 5 in gene GNAQ was 40 and 16.7%, in gene GNA11 - 0 and 50%, respectively. A significant association between rate of mutated glutamine at position 209 in gene GNAQ and high rate of retinal detachment (0.55 at p < 0.05) was found. Rate of mutations in exon 5 of gene GNA11 was fund to be higher by 2.8-fold in spindle-cell vs. epithelioid type tumor. Allele C of polymorphic marker C3435T in gene ABCB1 was found in 80% cases. Rate of predisposing genotype CC in patients with UM vs. control group was higher by 4-fold. Such genotype was associated with high risk of developing UM (relative risk 8.5; p = 7 x 10<sup>-6</sup>). A significant correlation between incidence rate of CC genotype of polymorphic marker C3435T in gene АBСB1 and height and pigmentation degree of the tumor (p = 0.0391 and p = 0.0381) as well as condition of vascular vessels and epithelioid/mixed cell type of UM (0.0493 and 0.0569) was observed. TT genotype was not found in UUM patients. Conclusions. High rate of mutations in genes GNAQ/GNA11 as well as association of allele C of polymorphic marker C3435T in gene ABCB1 with unfavorable clinical and morphological UM types were found. These data might be used in further studies for developing modern approaches for predicting course of UM as well as for screening UM risk group patients.