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Inactivation of Epigenetic Regulators due to Mutations in Solid Tumors

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Abstract

Main factors involved in carcinogenesis are associated with somatic mutations in oncogenes and tumor suppressor genes representing changes in the DNA nucleotide sequence. Epigenetic changes, such as aberrant DNA methylation, modifications of histone proteins, and chromatin remodeling, are equally important in the development of human neoplasms. From this perspective, mutations in the genes encoding key participants of epigenetic regulation are of particular interest including enzymes that methylate/demethylate DNA, enzymes that covalently attach or remove regulatory signals from histones, components of nucleosome remodeling multiprotein complexes, auxiliary proteins and cofactors of the above-mentioned molecules. This review describes both germline and somatic mutations in the key epigenetic regulators with emphasis on the latter ones in the solid human tumors, as well as considers functional consequences of these mutations on the cellular level. In addition, clinical associations of the somatic mutations in epigenetic regulators are presented, as well as DNA diagnostics of hereditary cancer syndromes due to germline mutations in the SMARC proteins and chemotherapy drugs directly affecting the altered epigenetic mechanisms for treatment of patients with solid neoplasms. The review is intended for a wide range of molecular biologists, geneticists, oncologists, and associated specialists.

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Abbreviations

BC:

breast cancer

lncRNAs:

long non-coding RNAs

miRNAs:

microRNAs

NGS:

next generation sequencing

NSCLC:

non-small-cell lung cancer, PC, prostate cancer

UBC:

urinary bladder cancer

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Funding

The work was financially supported by the Russian Foundation for Basic Research (project No. 18-29-09020) and by the State Budget Project of the Ministry of Science and Education of the Russian Federation for 2020.

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Authors and Affiliations

  1. Institute of Molecular Medicine, Sechenov First Moscow State Medical University (Sechenov University), 119991, Moscow, Russia

    M. V. Nemtsova, D. S. Mikhaylenko, E. B. Kuznetsova, I. I. Bykov & A. A. Zamyatnin Jr.

  2. Research Centre for Medical Genetics, 115478, Moscow, Russia

    M. V. Nemtsova & D. S. Mikhaylenko

  3. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991, Moscow, Russia

    A. A. Zamyatnin Jr.

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  1. M. V. Nemtsova
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  2. D. S. Mikhaylenko
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  3. E. B. Kuznetsova
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  4. I. I. Bykov
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Correspondence to D. S. Mikhaylenko.

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Nemtsova, M., Mikhaylenko, D., Kuznetsova, E. et al. Inactivation of Epigenetic Regulators due to Mutations in Solid Tumors. Biochemistry Moscow 85, 735–748 (2020). https://doi.org/10.1134/S0006297920070020

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  • DOI: https://doi.org/10.1134/S0006297920070020

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