The role of the <i>C3435T</i> polymorphic marker of the <i>ABCB1</i> gene in the development of early choroidal melanoma

The aim of the work is to find out how the ABCB1 C3435T polymorphism gene is associated with the risk of early choroid melanoma (ECM) and to study the genotypes distribution frequency of the ABCB1 polymorphic gene in ECM patients. Material and methods. The prospective study included 26 previously untreated ECM patients (7 men and 19 women) aged 32 to 80 (mean age 59.0 ± 14.3 years). All patients underwent general ophthalmological examinations and special instrumental diagnostics (ultrasound examination, spectral optical coherence tomography, OCT angiography). Monolateral ECM was diagnosed in 25 patients (96 %), bilateral ECM in 1 patient (4 %). In all, 27 eyes were affected. The material for the study was genomic DNA taken from peripheral blood leukocytes from patients with ECM. Genotyping was carried out using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results. Significant associations were found between (1) the CC genotype and the risk of ECM and (2) between the TT genotype and a low risk of tumor development. A reliable association of the CT genotype of the ABCB1 C3435T polymorphism gene with the presence of orange pigment on the tumoral surface and the familial cancer history of ECM patients was revealed. Conclusion. In the future, the obtained results can be used in the development of innovative approaches predicting the course of melanoma, and in patient screening

Association of clinical, instrumental and molecular genetic predictors with the risk of development and tumor progression of melanocytic intraocular neoplasms

Purpose: to analyze the frequency and possible associations of GNAQ and GNA11 oncogenes in peripheral blood ctDNA, as well as the relationship of the ABCB1/MDR1 rs1045642 polymorphic marker gene with the clinical and instrumental characteristics of nevi and initial choroidal melanoma. Material and methods. A prospective study of 81 previously untreated patients (84 eyes, mean age 57.8 ± 13.8 years) included general ophthalmological examinations and special instrumental diagnostics: ultrasound checkups, spectral optical coherent tomography (SOCT), OCT angiography. Depending on the nature of the pathology, the patients were divided into three groups: I — with benign choroidal nevus (23 eyes, 28 %; mean age 61.1 ± 13.6 years); II — with suspicious choroidal nevus (24 eyes, 29 %; mean age 54.8 ± 13.0 years); III — small choroidal melanoma (37 eyes, 43 %; mean age 56.2 ± 14.8 years). Genotyping was performed by melting curve analysis. Results. A significant association was revealed between the presence of ctDNA (GNAQ/GNA11 oncogenes) and the CC genotype of the ABCB1 gene with the risk of developing a small melanoma of the choroid and choroidal nevi. In patients with suspicious choroidal nevus, there is an unfavorable significance of mutations in the GNAQ/GNA11 genes (ctDNA). A relative unfavorable predictive significance of the presence of mutations in the GNAQ/GNA11 genes in peripheral blood ctDNA of patients with a benign choroidal nevus was suggested. No significant associations between GNAQ/GNA11 mutations, ABCB1 gene polymorphism and clinical/instrumental tumor features were found. Conclusion. The revealed features can be used for screening the patients with melanocytic intraocular tumors and for developing modern approaches to predicting the course of UM in the early preclinical period