THE ROLE OF MOLECULAR AND GENETIC FACTORS IN UVEAL MELANOMA PATHOGENESIS

S.V. Saakyan (1, 2), A.Iu. Tsygankov(2), A.G. Amiryan(1), V.I. Loginov(3)
1-Moscow Helmholtz Research Institute of Eye Diseases, Sadovaya-Chernogryazskaya str., 14/19, Moscow, 105062, Russian Federation;
2-Moscow State Medical Stomatological University, Delegatskaya str. 20/1, Moscow, 127473, Russian Federation;
3-Institute of General Pathology and Pathophysiology, Baltiiskaya str. 8, Moscow, 125315, Russian Federation
E-mail: alextsygankov1986@yandex.ru

Uveal melanoma (UM) is a rare, aggressive intraocular malignant tumor, leading to metastatic disease in more than 50% of patients. Cytogenetic and molecular studies have identified some genetic prognostic factors considered to be reliable to forecast the survival rate of UM patients. The review presents the basic molecular and genetic characteristics of uveal melanoma. Modern diagnostic methods of molecular genetic aberrations including fluorescence hybridization in situ, comparative genomic hybridization, quantitative PCR analysis, loss of heterozygosity, single nucleotide polymorphism analysis, and new generation sequencing are described. The basic chromosomal changes in UM, such as the loss of one copy (monosomy) of chromosome 3, deletion in the short arm of chromosome 1 and chromosome 8q duplication, and disorders involved in the molecular signaling pathways of UM oncogenesis, including RAS-RAF-MEK-ERK and PI3K-PTEN-AKT pathways, are listed. Changes in genes GNAQ/GNA11, BAP1 and other genes are considered in detail. These changes are important for the tumor development. Polymorphism of ABCB1 / MDR1 and its role in the pathogenesis of UM are described. Further research in this field discovers prospects for selective chemotherapy and immunotherapy of UM.
Keywords: 
uvealmelanoma, chromosomal aberrations, gene mutations, polymorphism