Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press38810.17650/2313-805X-2021-8-4-42-52REVIEW ARTICLESОБЗОРНЫЕ СТАТЬИThe role of retroelements in the development of hereditary tumor syndromesРоль ретроэлементов в развитии наследственных опухолевых синдромовhttps://orcid.org/0000-0002-4091-382XMustafinR. N.МустафинР. Н.
Russian Federation

Rustam Nailevich Mustafin

3 Lenin St., Ufa 450008

Рустам Наилевич Мустафин

450008 Уфа, ул. Ленина, 3

ruji79@mail.ruhttps://orcid.org/0000-0003-2987-3334KhusnutdinovaE. K.ХуснутдиноваЭ. К.
Russian Federation

71 Prospekt Oktyabrya, Ufa 450054

450054 Уфа, пр-т Октября, 71

Bashkir State Medical UniversityФГБОУ ВО «Башкирский государственный медицинский университет»Institute of Biochemistry and Genetics of the Ufa Federal Research Center of Russian Academy of SciencesИнститут биохимии и генетики ФГБНУ «Уфимский федеральный исследовательский центр» Российской академии наук151220218442521812202118122021Copyright ©; 2021, Mustafin R.N., Khusnutdinova E.K.Copyright ©; 2021, Мустафин Р.Н., Хуснутдинова Э.К.2021Mustafin R.N., Khusnutdinova E.K.Мустафин Р.Н., Хуснутдинова Э.К.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/388

Genomic instability caused by activated retroelements plays an important role in the development of malignant neoplasms. Activated retroelements cause enhanced expression of oncogenes containing transposon sequences in their promoters and introns. Oncosuppressor genes contain hot spots of insertional mutagenesis, therefore retroelements cause their inactivation. As a result, genomic instability increases during the development of tumors, since oncosuppressors normally silence retrotransposons. Accordingly, inactivation of the oncosuppressor causes increased expression of retroelements.

The study objective is to describe the role of retrotransposons on the development of hereditary tumor syndromes, which will allow a new look at the classical concepts of carcinogenesis. The data we have described allow us to consider in a new way the Knudson’s two-hit hypothesis in hereditary tumor syndromes, since the germinal inactivation of 1 allele of the oncosuppressor gene promotes the development of malignant tumors due to an increase in the activity of transposons. The consequence of the developed instability in the tumor is the inactivation of the second allele of the oncosuppressor gene, which contributes to clonal evolution and the progression of carcinogenesis.

В развитии злокачественных новообразований большую роль играет геномная нестабильность, обусловленная активированными ретроэлементами. Происходит усиленная экспрессия онкогенов, которые содержат последовательности транспозонов в промоторах и интронах. При этом гены онкосупрессоров инактивируются, поскольку содержат горячие точки инсерционного мутагенеза. В то же время ретроэлементы содержат последовательности, чувствительные к негативному регуляторному влиянию онкосупрессоров. Поэтому их инактивация усиливает геномную нестабильность при канцерогенезе вследствие устранения сайленсинга ретроэлементов.

Цель статьи – описать механизмы влияния ретротранспозонов на развитие наследственных опухолевых синдромов, что позволит по-новому рассмотреть классические представления канцерогенеза.

Представленные данные позволяют пересмотреть двухударную гипотезу Кнудсона при наследственных опухолевых синдромах, поскольку герминативная инактивация 1 аллеля онкосупрессорного гена способствует развитию злокачественных опухолей из-за повышения активности транспозонов. Соматическая инактивация 2-го аллеля является не причиной, а следствием развившейся в неоплазме геномной нестабильности и может влиять на клональную эволюцию и прогрессирование канцерогенеза.

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