THE ANALYSIS OF RASSF1A AND SEMA3B TUMOR SUPRESSOR GENES CPG-ISLANDS METHYLATION STATUS IN UVEAL MELANOMA PATIENTS

DOI: https://doi.org/10.29296/24999490-2018-01-09

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

Introduction. Uveal melanoma (UM) is a tumor of neuroectodermal origin developing from melanocytes of the uveal tract. The very common pathological characteristic of UM is its metastatic activity in liver, leading to the poor efficiency of the treatment. That`s why there is a need to find new molecular genetic biomarkers that can be involved in UM pathogenesis. As an example of such biomarker it could be abnormal methylation status of RASSF1A and SEMA3B suppressor genes. The aim of the study. The analysis of the frequency of the methylation in promoter regions in tumor suppressor genes RASSF1A and SEMA3B, association with UM progression Methods. In scope of our work we use for studying 30 patients with histologically proved diagnosis of UM. In all cases, enucleation of the affected eye was performed. DNA was isolated by standard phenol-chloroform extraction method. The methylation of RASSF1A and SEMA3B genes promoter regions were determined by methyl-sensitive restriction analysis. Results. The frequency of CpG-island methylation in RASSF1A gene –26,7% – in tumors was shown to be higher if compared with histologically normal of choroid tissue – 3,3% – (p=0,026). A statistically significant correlation of the methylation in RASSF1A gene promoter region with the most favorable spindle morphological UM subtype (p=0,049), decreased tumor height (p=0,018) and also with reducing acoustic density in the apex of the tumor by ultrasound duplex scanning results (p=0,05) were shown also. No methylation of the SEMA3B gene promoter region in all cases was determined. Conclusion. Our findings show the important role of the methylation in the RASSF1A gene promoter region to be the favourable prognostic factor for the UM development. The role of the methylation in the SEMA3B gene promoter region in UM development is not confirmed.
Keywords: 
uveal melanoma, methylation, RASSF1A, SEMA3B

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