surgoncoКреативная хирургия и онкологияCreative surgery and oncology2076-30932307-0501Башкирский государственный медицинский университет10.24060/2076-3093-2021-11-2-157-165surgonco-586Research ArticleОБЗОР ЛИТЕРАТУРЫREVIEWSГенетические предикторы развития злокачественных новообразований (обзор литературы)Genetic Predictors of Malignancy: a Literature ReviewПушкаревА. В.PushkarevA. V.

Пушкарев Алексей Васильевич — хирургическое отделение № 5

Россия, Республика Башкортостан, Уфа

Aleksey V. Pushkarev — Surgery Unit No. 5

Ufa, Russian Federation

ГалеевМ. Г.GaleevM. G.

Галеев Марат Галиакбарович — к.м.н., хирургическое отделение № 5

Россия, Республика Башкортостан, Уфа

Marat G. Galeev — Cand. Sci. (Med.), Surgery Unit No. 5

Ufa, Russian Federation

https://orcid.org/0000-0001-5569-2321ПушкаревВ. А.PushkarevV. A.

Пушкарев Василий Александрович — д.м.н., отделение № 8

Россия, Республика Башкортостан, Уфа

Vasiliy A. Pushkarev — Dr. Sci. (Med.), Unit No. 8

Ufa, Russian Federation

doctorpushkarev@mail.ruhttps://orcid.org/0000-0003-0996-5995СултанбаевА. В.SultanbaevA. V.

Султанбаев Александр Валерьевич — к.м.н., отдел противоопухолевой лекарственной терапии

Россия, Республика Башкортостан, Уфа

Aleksandr V. Sultanbaev — Cand. Sci. (Med.), Anticancer Drug Therapy Unit

Ufa, Russian Federation

Республиканский клинический онкологический диспансерРоссияRepublican Clinical Oncological DispensaryRussian Federation202122052021112157165Copyright © Пушкарев А.В., Галеев М.Г., Пушкарев В.А., Султанбаев А.В., 20212021Пушкарев А.В., Галеев М.Г., Пушкарев В.А., Султанбаев А.В.Pushkarev A.V., Galeev M.G., Pushkarev V.A., Sultanbaev A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.surgonco.ru/jour/article/view/586

В статье представлен обзор литературы за последние годы, где рак расценивают как генетическое заболевание, способное манифестировать как спорадическими случаями, так и быть наследственным, сопровождающимся различными мутациями в геноме или перестройками на уровне ДНК. Данные изменения могут проявляться в точковых мутациях, хромосомных аберрациях, гиперметилировании, что приводит к дефектам репарации ДНК. Дефекты генов-супрессоров опухолевого роста (BRCA1, BRCA2, CHEK2, PTCH1 и др.) являются причиной наследственной предрасположенности развития рака молочной железы (РМЖ) и рака яичников (РЯ), обусловленной нарушениями стабильности генома. Выявление соматических мутаций имеет большое значение в изучении механизма канцерогенеза и поиска выбора правильного лечения. Из-за гетерогенности рака идентификация мутаций из опухоли является сложной задачей. Выбор тактики лечения и ее эффективность при РМЖ и РЯ зависят от наличия в опухолевых клетках дефицита гомологичной рекомбинации, обусловленной чаще всего дефектом генов BRCA1/2. CHEK2-ассоциированные новообразования составляют большую долю наследственного РМЖ, механизмы формирования их связаны с дефектами системы репарации ДНК. Избыточная экспрессия белка PTCH 1 является мишенью для опухолей молочной железы, легкого, яичников, толстой кишки и др.

Таким образом, генетические исследования коренным образом изменили представления об этиологии и патогенезе злокачественных опухолей у человека. Распознавание молекулярного фенотипа онкозаболеваний служит важнейшим прогностическим фактором болезни и дает возможность персонифицировать лечение больных.

The review covers recent research on cancer as a genetic disease manifesting both sporadically and in germline through variant genomic mutations or DNA rearrangements. This change can be point mutations, chromosomal aberrations or hypermethylation leading to DNA repair failures. Defects in tumour suppressor genes (BRCA1, BRCA2, CHEK2, PTCH1, etc.) underly hereditary predisposition to breast cancer (BC) and ovarian cancer (OC) due to genome instability. Studying somatic mutations is key to the understanding of carcinogenesis mechanisms and finding apt therapies. Heterogeneity of cancers renders the tumour mutation profiling uneasy. The treatment choice and efficacy in BC and OC depends on homologous recombination defects in tumour cells usually imposed by damaged BRCA1/2 genes. CHEK2- associated neoplasms account for most hereditary BCs linked to flaws in the DNA repair machinery. Overexpression of the PTCH1 protein is the target in breast, lung, ovarian, colonic cancers, etc.

Genetic research has fundamentally altered our understanding of the aetiology and pathogenesis of human malignancy. The molecular cancer phenotype is of paramount importance in the disease prognosis and treatment personalisation.

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The authors declare that there are no conflicts of interest present.