oncopatОнкопатологияONCOPATHOLOGY2618-70193034-353410.63769/2618-7019-2026-9-3-10-20oncopat-89Research ArticleПЕРЕДОВАЯ СТАТЬЯLEADING ARTICLEНаследственные патогенные варианты в гене PALB2Inherited pathogenic variants in the PALB2 genehttps://orcid.org/0000-0003-2213-5785СендеровичА. И.SenderovichA. I.

Сендерович Анастасия Ильинична.

121352 Москва, ул. Староволынская, 10; 105425 Москва, 3-я Парковая ул., 51, стр. 1; 121359 Москва, ул. Маршала Тимошенко, 15

Anastasiya I. Senderovich.

10 Starovolynskaya St., Moscow 121352; Build. 1, 51 3rd Parkovaya St., Moscow 105425; 15 Marshala Timoshenko St., Moscow 121359

a.senderovich@mail.ruhttps://orcid.org/0000-0003-4775-3299ЛюбченкоЛ. Н.LyubchenkoL. N.

121352 Москва, ул. Староволынская, 10; 105425 Москва, 3-я Парковая ул., 51, стр. 1; 125284 Москва, 2-й Боткинский пр-д, 3

10 Starovolynskaya St., Moscow 121352; Build. 1, 51 3rd Parkovaya St., Moscow 105425; 3 2nd Botkinskiy Proezd, Moscow 125284

ПодберезинаЮ. Л.PodberezinaYu. L.

121352 Москва, ул. Староволынская, 10

10 Starovolynskaya St., Moscow 121352

ЖуравлевС. В.ZhuravlevS. V.

121352 Москва, ул. Староволынская, 10

10 Starovolynskaya St., Moscow 121352

ФГБУ «Клиническая больница № 1» Управления делами Президента Российской Федерации; Научно-исследовательский институт урологии и интервенционной радиологии им. Н.А. Лопаткина – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава России; ФГБУ «Центральная клиническая больница с поликлиникой» Управления делами Президента Российской ФедерацииРоссияClinical Hospital No. 1 of the Presidential Administration of the Russian Federation; N.A. Lopatkin Research Institute of Urology and Interventional Radiology – branch of the National Medical Research Radiological Center, Ministry of Health of Russia; Central Clinical Hospital with Polyclinic of the Presidential Administration of the Russian FederationRussian FederationФГБУ «Клиническая больница № 1» Управления делами Президента Российской Федерации; Научно-исследовательский институт урологии и интервенционной радиологии им. Н.А. Лопаткина – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава России; ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава РоссииРоссияClinical Hospital No. 1 of the Presidential Administration of the Russian Federation; N.A. Lopatkin Research Institute of Urology and Interventional Radiology – branch of the National Medical Research Radiological Center, Ministry of Health of Russia; National Medical Research Radiological Center, Ministry of Health of RussiaRussian FederationФГБУ «Клиническая больница № 1» Управления делами Президента Российской ФедерацииРоссияClinical Hospital No. 1 of the Presidential Administration of the Russian FederationRussian Federation202614102026931020Copyright © Сендерович А.И., Любченко Л.Н., Подберезина Ю.Л., Журавлев С.В., 20262026Сендерович А.И., Любченко Л.Н., Подберезина Ю.Л., Журавлев С.В.Senderovich A.I., Lyubchenko L.N., Podberezina Y.L., Zhuravlev S.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://oncopat.elpub.ru/jour/article/view/89

Ген PALB2 кодирует ключевой белок, участвующий в наиболее точном механизме репарации двунитевых разрывов ДНК – гомологичной рекомбинации. PALB2 действует как связующее звено между белками BRCA1 и BRCA2, обеспечивая формирование функционального BRCA-комплекса и стимулируя инвазию цепи белком RAD51. Герминальные патогенные варианты в гене PALB2 являются фактором предрасположенности к наследственному раку со средней и высокой пенетрантностью. Мутации значительно повышают риск развития рака молочной железы, являясь 3-м по распространенности геном риска после BRCA1 и BRCA2, с кумулятивным риском до 52,8 % к 80 годам. Кроме того, мутации PALB2 ассоциированы с повышенным риском рака яичников, поджелудочной и предстательной желез. Биаллельные мутации вызывают анемию Фанкони. Особое клиническое значение мутаций PALB2 заключается в их терапевтической предсказательной роли. Наличие герминальных патогенных вариантов в PALB2 является определяющим маркером чувствительности опухолей к PARP-ингибиторам, таким как олапариб, талазопариб и рукапариб, что подтверждается высокими показателями объективного ответа в клинических исследованиях при раке молочной, предстательной и поджелудочной желез.

Таким образом, комплексное генетическое тестирование, включающее PALB2, становится необходимым элементом современной онкологической практики для геноспецифической оценки риска, персонализации профилактических стратегий и оптимизации тактики лечения за счет применения таргетной терапии.

The PALB2 gene encodes a key protein involved in the most accurate mechanism of DNA double-strand break repair – homologous recombination. PALB2 acts as a link between the BRCA1 and BRCA2 proteins, ensuring the formation of a functional BRCA-complex and stimulating strand invasion by the RAD51 protein. Germline pathogenic variants in the PALB2 gene are a predisposition factor for hereditary cancer with moderate-to-high penetrance. Mutations significantly increase the risk of developing breast cancer (BC), being the third most common risk gene after BRCA1 and BRCA2, with a cumulative risk of up to 52.8 % by age 80. Furthermore, PALB2 mutations are associated with an elevated risk of ovarian, pancreatic, and prostate cancers. Biallelic mutations cause Fanconi anemia. The special clinical significance of PALB2 mutations lies in their therapeutic predictive role. The presence of germline pathogenic variants in PALB2 is a defining marker of tumor sensitivity to PARP inhibitors, such as olaparib, talazoparib, and rucaparib, which is confirmed by high objective response rates in clinical trials for BC, prostate, and pancreatic cancers.

Thus, comprehensive genetic testing that includes PALB2 is becoming a necessary element of modern oncological practice for gene-specific risk assessment, personalization of prophylactic strategies, and optimization of treatment tactics through the use of targeted therapy.

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