Увеальная меланома -опухоль нейроэктодермального происхождения, развивающаяся из меланоцитов увеаль-ного тракта (хориоидеи, цилиарного тела, радужки). Это заболевание является редкой разновидностью мелано-мы, составляя приблизительно 3,5% от всех зарегистрированных случаев меланомы. И если в лечении метаста-тической меланомы кожи уже достигнуты значительные успехи, созданы и зарегистрированы ингибиторы тирозинкиназ BRAF и MEK (вемурафениб, дабрафениб, траметиниб и др.) и моноколональные антитела для бло-кирования CTLA-4, PD-1 и PD-L1 (ипилимумаб, ламбролизумаб, ниволумаб и др.), то для увеальной меланомы активно ведут поиск новых мишеней направленной противоопухолевой терапии.Ключевые слова: увеальная меланома, мутации в генах GNAQ и GNA11, метастазирование, лечение. Uveal melanoma -a tumor of neuroectodermal origin that develops from melanocytes of uveal tract (choroid, ciliary body, iris). In routine practice of oncologist the uveal melanoma is uncommon disease. This disease is a rare variant of melanoma, accounting for about 3.5% of all reported cases of melanoma. Uveal melanoma differs from cutaneous melanoma and mucosal melanoma as the clinical course (later metastasis from a primary lesion of the liver), and on the molecular -biological properties (low frequency of mutations in the genes BRAF and NRAS, mutations in genes GNAQ and GNA11). And if in the treatment of metastatic melanoma has already achieved considerable success, to create and register tyrosine kinase inhibitors BRAF and MEK (vemurafenib, dabrafenib, trametinib) and monoclonal antibodies to block the receptor CTLA-4 and PD-1 protein (ipilimumab, nivolumab), for uveal melanoma are actively searching for new targets aimed anticancer therapy.Keywords: uveal melanoma, metastasis, treatment, mutations in genes GNAQ and GNA11.Среди злокачественных опухолей глаза меланома является самой распространенной опухолью. Меланома глаза может встречаться в защитном аппарате глазного яблока (верхнее и нижнее веки, глазница), в придаточном аппа-рате глаза (слезная железа, ее протоки и конъ-юнктива) и в сосудистом тракте глаза. Около 97% всех глазных меланом приходится на сосу-дистый (увеальный) тракт глаза (передний -радужка и задний -цилиарное тело и хорио-

Контакты: Давид Романович Насхлеташвили nas-david@yandex.ruЭффективность традиционной химиотерапии (темозоломид, фотемустин, ломустин)

Purpose of the study: to analyze characteristics of cancer-testis antigens (Ctas) as potential biomarkers for dissemination of primary human skin melanoma (sm).Material and Methods. Recent publications from Pubmed, scopus and elibrary databases were analyzed for the available appropriate literature review. In total, 176 papers reported the description of Ctas and encoding genes and their potential for prognosis of primary sm dissemination. The authors included 52 of them in the given review.Results. Two sections of the paper comprise clinically significant characteristics of Ctas and their genes, including overexpression, which is selective for the heterogeneous tumor cell populations and mediated by humoral and/or cellular immune reactions; the association of tumor process and activation of Cta genes by demethylation of promotor sites, which is correlated with tumor progression; and the conditions required for effective immunotherapy involving Ctas and/or their genes.Conclusion. At present, there are no standards or clinical recommendations for the Cta-based prognosis of the early dissemination of primary skin melanoma. Therefore, it is important to study and analyze the Cta and encoding gene characteristics that reveal the connection between primary sm progression and tumor genesis including the role of circulating tumor cells (ctc), similar to stem cells, which have epithelial-mesenchymal transition (emt) phenotype, for clinical diagnostics of early sm dissemination. As a result of the study, the following Ctas could be considered as significant biomarkers of the early sm dissemination: mage-a1, mage-a4 and ny-eso-1, which expression correlates with the clinical pathological description of the disease progression, as well as with the relapse-free period and overall survival of the patients; magea3, which expression correlates with spag5 activation and Cd8+ t-cell abundance; ssx, a marker for stem cell migration including identification of the cells with emt and/or ctcs; and prame, signaling marker for dissemination of the uveal melanoma.

Background. Ocular melanoma is the most common cancer of adult eye and is represented by two main subtypes of uveal (UM) and conjunctival (CM) melanoma with distinct clinical (frequency, localization, histology) and genomic features. The objective is to compare molecular and genetic characteristics of tumors in patients with melanoma of the eye. Materials and methods. In this study molecular profiling of 78 tumors including 73 UM (choroidea, ciliar body and iris) and 5 СM, was evaluated. DNA was isolated from tumor cells collected by macrodissection of FEPE sections of tumor biopsies using proteinase K. The following genes were studied by Sanger sequencing: GNAQ, GNA11, KIT, BRAF, NRAS. Results. Mutations in GNAQ and GNA11 were found in 81 % (59/73) of UM, in 42 % (31/73) and 38 % (28/73) of cases correspondently. GNAQ mutations were more frequent in primary UM (63 %), while GNA11 mutations dominated in metastatic UM (42 %). There was а correlation between frequency of GNAQ/GNA11 mutations and histologic type of UM. GNAQ mutations were identified in 55 % of spindle cell UM, while GNA11 mutations were more frequent in epithelioid cell UM (42 %). There were no differences in frequency of GNAQ/GNA11 mutations in UM of patients of different age (younger and elder 50 years). There was no statistically difference in UM patient outcome with GNAQ or GNA11 mutations. We also detected 3 UM with KIT mutations and 2 UM with BRAF mutations. There was no big difference in frequency of «driver mutations» in UM of choroidea, ciliar body and iris. Molecular profiling of conjunctival melanoma (CM) resembles that of cutaneous melanoma of skin: in 3 (60 %) CM BRAF V600E was identified and in 1 (20 %) – NRAS Q61K. Conclusion. Genetic analysis reveals wide diversity of melanoma of eye and is important for it characterization and treatment.

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