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Bulletin of Experimental Biology and Medicine

, Volume 168, Issue 3, pp 366–370 | Cite as

System of Markers Based on the Methylation of a Group of Proapoptotic Genes in Combination with MicroRNA in the Diagnosis of Breast Cancer

  • E. A. BragaEmail author
  • A. M. Burdennyy
  • I. V. Pronina
  • E. A. Filippova
  • T. P. Kazubskaya
  • M. V. Fridman
  • D. S. Khodyrev
  • A. V. Karpukhin
  • V. I. Loginov
  • N. E. Kushlinskii
Article
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Systems of markers for the diagnosis of breast cancer based on DNA methylation of a group of suppressor protein-coding genes, hypermethylated microRNA genes, and their combinations were compiled. On a representative sample of 70 paired breast cancer specimens (tumor/normal), MS-PCR analysis revealed a significant increase in the methylation frequency of 5 protein-coding genes: RASSF1A suppressor and apoptosis genes APAF1, BAX, BIM/BCL2L11, and DAPK1 (34-61% vs. 4-24%) and 6 microRNA genes: MIRG124G1, MIRG125bG1, MIRG129G2, MIRG148a, MIRG34b/c, and MIRG9G3 (36-76% vs. 6-27%). ROC-analysis showed that a combination of 4 genes (APAF1, BAX, BIM/BCL2L11, and DAPK1) and MIRG125bG1 gene constitute a highly efficient 5-marker system with 100% specificity and sensitivity of 94-96% at AUC=0.98-0.97, suitable also for patients with stage I and II breast cancer. Detection of methylation of at least one gene in this system in biopsy or postoperative material is sufficient to refer the sample to breast cancer.

Key Words

proapoptotic genes microRNAs methylation breast cancer diagnostic marker systems 

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • E. A. Braga
    • 1
    • 2
    Email author
  • A. M. Burdennyy
    • 1
    • 3
  • I. V. Pronina
    • 1
  • E. A. Filippova
    • 1
  • T. P. Kazubskaya
    • 4
  • M. V. Fridman
    • 5
  • D. S. Khodyrev
    • 6
  • A. V. Karpukhin
    • 2
  • V. I. Loginov
    • 1
    • 2
  • N. E. Kushlinskii
    • 4
  1. 1.Research Institute of General Pathology and PathophysiologyMoscowRussia
  2. 2.N. P. Bochkov Research Center of Medical GeneticsMoscowRussia
  3. 3.N. M. Emanuel Institute for Biochemical PhysicsRussian Academy of SciencesMoscowRussia
  4. 4.N. N. Blokhin National Medical Research Center of OncologyMinistry of Health of the Russian FederationMoscowRussia
  5. 5.N. I. Vavilov Institute of General GeneticsRussian Academy of SciencesMoscowRussia
  6. 6.Federal Research Clinical Center of Specialized Types of Medical Care and Medical Technologies of Federal Medical-Biological Agency of RussiaMoscowRussia

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