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Vol 53(2019) N 3 p. 371-378; DOI 10.1134/S0026893319030051 Full Text

E.A. Filippova1, V.I. Loginov1,2, I. V. Pronina1, D.S. Khodyrev3, A.M. Burdennyya, T.P. Kazubskaya4, E.A. Braga1,2*

A Group of Hypermethylated miRNA Genes in Breast Cancer and Their Diagnostic Potential

1Institute of General Pathology and Pathophysiology, Moscow, 125315 Russia
2Research Center of Medical Genetics, Moscow, 115478 Russia
3Federal Research Clinical Center of Specialized Types of Medical Care and Medical Technologies, Federal Medico-Biological Agency of Russia, Moscow, 115682 Russia
4Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, 115478 Russia

*eleonora10_45@mail.ru
Received - 2018-11-29; Revised - 2018-12-12; Accepted - 2018-12-12

miRNA genes play an important role in cancer pathogenesis, while they may be suppressed by hypermethylation. Here, we assess the diagnostic potential of a group of hypermethylated miRNA genes (MIR-124-1, MIR-124-3, MIR-125B-1, MIR-127, MIR-132, MIR-193a, and MIR-34b/c) in a representative set of 70 breast cancer samples and 17 breast tissue samples from deceased donors with no malignancies. For these seven genes, the methylation status is determined using the methylation-specific PCR. Methylation reached 26-76% in tumor specimens, 1-27% in paired considered normal breast tissues, and 0-18% in breast tissue from deceased donors. By quantitative RT-PCR, reduced expression levels of the investigated miRNAs are detected, with a negative correlation of expression levels with gene hypermethylation. Combinations of three or four hypermethylation biomarkers, namely, MIR-124-1, MIR-125B-1, MIR-127, and MIR-34b/c are found suitable for breast cancer diagnostics; with sensitivity (76-93%), specificity (88-100%), and AUC (0.88-0.94). Notably, the MIR-127 gene was hypermethylated only in the tumor samples of patients with metastases, and, therefore, should be tested as a marker of breast cancer dissemination. These findings may lead to improvement in the management of breast cancer.

breast cancer, miRNA genes, hypermethylation, diagnostic markers, metastasis marker, MIR-127



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