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Vol 54(2020) N 2 p. 178-184; DOI 10.1134/S0026893320010057 Full Text

A.A. Dmitriev1*, A.D. Beniaminov1, N.V. Melnikova1, E.N. Pushkova1, G.V. Gerashchenko2, A.V. Kudryavtseva1, V.I. Kashuba2,3

Functional Hypermethylation of ALDH1L1, PLCL2, and PPP2R3A in Colon Cancer

1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
2Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kiev, 03680 Ukraine
3MTC, Biomedicum, Karolinska Institutet, Stockholm, 17165 Sweden

*Alex_245@mail.ru
Received - 2019-04-30; Revised - 2019-06-28; Accepted - 2019-06-28

DNA hypermethylation and mutations are key mechanisms for the downregulation of tumor suppressor genes. NotI-microarrays allowed us to detect hypermethylation and/or deletions in 180 NotI sites associated with 188 genes of human chromosome 3, in 24 paired (tumor/normal) colon samples. The most frequent aberrations (in more than 20% of tumor samples) were detected in the promoter regions of 20 genes. Expression and promoter methylation of these genes were analyzed using the data for paired colon samples from The Cancer Genome Atlas project. Three genes - ALDH1L1, PLCL2, and PPP2R3A - revealed a more than two-fold average decrease in expression and a negative correlation between mRNA level and promoter hypermethylation. The expression of these three genes was then evaluated in 30 paired colon samples by quantitative PCR. Frequent (in more than 60% of cases) and significant (5-9-fold on average) mRNA level decrease was found for each of the genes in the tumor samples. The results indicate a suppressor role of the ALDH1L1, PLCL2, and PPP2R3A genes in colon cancer, as well as functional significance of hypermethylation in the downregulation of these genes.

DNA methylation, colon cancer, tumor suppressor genes



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