METHYLATION INVOLVEMENT IN REGULATION OF EXPRESSION OF FUNCTIONALLY SIGNIFICANT GENES ON CHROMOSOME 3: RHOA, GPX1, USP4, DAG1, NKIRAS1 IN BREAST CANCER

V.I. Loginov (1), I.V. Pronina (1), A.M. Burdennyy (1), D.S. Khodyrev (2), T.P. Kazubskaya (3), E.A. Braga (1), A.A. Kubatiev (1), N.E. Kushlinskii (3)
1 -Institute of General Pathology and Pathophysiology, Baltiyskaya str., 8, Moscow, Russian Federation, 125315;
2 -Federal Research Clinical Center of specialized types of medical care and medical technologies, Orekhovyy bul'var, 28, Moscow, Russian Federation, 115682;
3 -N.N. Blokhin Russian Cancer Research Center, Kashirskoe shosse, 24, Moscow, Russian Federation, 115478

Introduction. Epigenetic changes caused by methylation in promoter CpG-islands are a fine and dynamic mechanism of gene expression regulation in tumors. Increased and decreased expression and alterations in the methylation status of the gene are considered to be primary criteria for oncogenic or suppressor gene function and prediction of cancer. The aim of the study. The assessment of the methylation contribution in the regulation of the expression of the functionally important genes on chromosome 3; the identification of new genes with features of oncogenes or tumor suppressors in breast cancer as prognostic markers.Methods. Samples of tumor and surrounding histologically normal tissues from 69 patients with breast cancer were collected and clinically characterized. The level of mRNA was determined by semiquantitative RT-PCR. DNA methylation analysis was performed using two methyl-sensitive restriction endonucleases HpaII and HhaI with following PCR. Results. For the first time there was studied and shown the dual role of methylation of GPX1, NKIRAS1, RHOA, DAG1 and USP4 with a prevalence of cases with increased expression, that is characteristic feature of oncogenes. There was established the significant correlation (p
Keywords: 
regulation of gene expression, methylation/demethylation, breast cancer