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Успехи молекулярной онкологии

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Роль ретроэлементов в развитии наследственных опухолевых синдромов

https://doi.org/10.17650/2313-805X-2021-8-4-42-52

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Аннотация

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.

Об авторах

Р. Н. Мустафин
ФГБОУ ВО «Башкирский государственный медицинский университет»
Россия

Рустам Наилевич Мустафин

450008 Уфа, ул. Ленина, 3



Э. К. Хуснутдинова
Институт биохимии и генетики ФГБНУ «Уфимский федеральный исследовательский центр» Российской академии наук
Россия

450054 Уфа, пр-т Октября, 71



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Для цитирования:


Мустафин Р.Н., Хуснутдинова Э.К. Роль ретроэлементов в развитии наследственных опухолевых синдромов. Успехи молекулярной онкологии. 2021;8(4):42-52. https://doi.org/10.17650/2313-805X-2021-8-4-42-52

For citation:


Mustafin R.N., Khusnutdinova E.K. The role of retroelements in the development of hereditary tumor syndromes. Advances in Molecular Oncology. 2021;8(4):42-52. (In Russ.) https://doi.org/10.17650/2313-805X-2021-8-4-42-52

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