Biopolym. Cell. 2021; 37(1):23-32.
Biomedicine
Methylation pattern of tumor-suppressor gene promoters as putative noninvasive diagnostic markers for prostate cancer
1Mankovska O. S., 2Korsakova A. S., 2Cherniavskyi K. R., 3Kononenko O. A., 3Stakhovskyy E. O., 4Bondarenko Yu. M., 1, 5Kashuba V. I., 1Gerashchenko G. V.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03143
  2. Educational and Scientific Center "Institute of Biology and Medicine",
    Taras Shevchenko National University of Kyiv
    64/13, Volodymyrska Str., Kyiv, Ukraine, 01601
  3. National Cancer Institute
    33/43, Lomonosova Str., Kyiv, Ukraine, 03022
  4. State Institution «Institute of Urology of NAMS of Ukraine»
    9-a, Yu. Kotsubyns'koho Str., Kyiv, Ukraine, 04053
  5. Karolinska Institutet
    Stockholm SE-171 77, Sweden

Abstract

Aim. To assess the rate of promoter methylation of putative TSGs for PCa in tumor tissue and in urine of PCa patients for better understanding of regulation of gene expression upon the PCa development and to evaluate the possibility to use the data on TSGs’ methylation for the development of noninvasive PCa markers. Methods. A quantitative methyl-specific PCR (qMSP) was used for the analysis of a methylation rate in prostate tissues and cell lines, and an ordinary MSP was performed for the study of urine samples. Results. We found that the RASSF1A promoter demonstrated a higher methylation rate in the TMPRSS2:ERG fusion positive PCa. The methylation of NKX3.1, PTEN and RASSF1A in DNA from urine was more common for cancer patients than for healthy donors. The promoters of CDH1 and GDF15 were methylated more frequently in PCa patients, than in patients with inflammatory disease. Conclusions. The abovementioned five genes can form a panel for early non-invasive detection of PCa. This set can be combined with the detection of the TMPRSS2:ERG fusion transcript. More work should be done to understand the molecular mechanisms explaining the functional role of promoter methylation of the selected genes.
Keywords: gene promoter methylation, tumor suppressor genes, noninvasive diagnostics, prostate cancer

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