cancerspЮжно-Российский онкологический журнал/ South Russian Journal of CancerSouth Russian Journal of Cancer2686-9039АНО "Перспективы онкологии"10.37748/2686-9039-2025-6-4-4FVFBDUcancersp-370Research ArticleОбмен опытомEXCHANGE OF EXPERIENCEМутация CHEK2 p.Ile157Thr (c.470T>C) при немелкоклеточном раке легкого: региональный опытCHEK2 p.Ile157Thr (c.470T>C) mutation in non-small cell lung cancer: regional experiencehttps://orcid.org/0000-0002-5918-4225СигалА. М.SigalA. M. 

 

Сигал Альберт Мойшевич – к.м.н., доцент кафедры хирургии ФГАОУ ВО «Казанский (Приволжский) федеральный университет», г. Казань, Российская Федерация; торакальный хирург, врач-онколог онкологического отделения №1 ГАУЗ «Республиканский клинический онкологический диспансер МЗ Республики Татарстан им. проф. М.З. Сигала», г. Казань, Российская Федерация

ORCID: https://orcid.org/0000-0002-5918-4225, eLibrary SPIN: 6457-2742, AuthorID: 909681

 

Albert M. Sigal – Cand. Sci. (Medicine), Associate Professor of the Department of Surgery, Kazan Federal University, Kazan, Russian Federation; thoracic surgeon, oncologist of the Oncology Department No. 1, The Republican Clinical Oncological Dispensary named after Prof. M.Z. Sigal, Kazan, Russian Federation

ORCID: https://orcid.org/0000-0002-5918-4225, eLibrary SPIN: 6457-2742, AuthorID: 909681

Sigal2@mail.ruhttps://orcid.org/0000-0002-3848-865XГордиевМ. Г.GordievM.  G. 

 

Гордиев Марат Гордиевич – к.м.н., заведующий лабораторией генетики ГБУЗ «Московский научно-практический центр лабораторных исследований» Департамента здравоохранения, г. Москва, Российская Федерация

ORCID: https://orcid.org/0000-0002-3848-865X, eLibrary SPIN: 8388-3566, AuthorID: 847417, Scopus Author ID: 55443225000

 

Marat G. Gordiev – Cand. Sci. (Medicine), Head of the Genetics Laboratory, Moscow Scientific and Practical Center for Laboratory Research, Moscow, Russian Federation

ORCID: https://orcid.org/0000-0002-3848-865X, eLibrary SPIN: 8388-3566, AuthorID: 847417, Scopus Author ID: 55443225000

marat7925@gmail.comhttps://orcid.org/0009-0002-4478-0443МостюковБ. Ф.MostyukovB. F. 

 

Мостюков Булат Фаридович – врач-ординатор кафедры онкологии, радиологии и паллиативной медицины ФГБОУ ВО «Казанская государственная медицинская академия» – филиал ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской Федерации, г. Казань, Российская Федерация

ORCID: https://orcid.org/0009-0002-4478-0443

 

Bulat F. Mostyukov – MD, resident physician of the Department of Oncology, Radiology and Palliative Medicine, Kazan State Medical Academy – Branch Campus of the Russian Medical Academy of Continuous Professional Education, Kazan, Russian Federation

ORCID: https://orcid.org/0009-0002-4478-0443

bulat-most@yandex.ruhttps://orcid.org/0009-0000-9791-9619СаттароваН. З.SattarovaN. Z. 

 

Саттарова Наталья Зиннуровна – врач-ординатор по специальности «Онкология» кафедры хирургии Института фундаментальной медицины и биологии ФГАОУ ВО «Казанский (Приволжский) федеральный университет», г. Казань, Российская Федерация

ORCID: https://orcid.org/0009-0000-9791-9619

 

Natalia Z. Sattarova – resident physician in the specialty "Oncology" of the Department of Surgery of the Institute of Physiotherapy and Biomedical Sciences, Kazan Federal University, Kazan, Russian Federation

ORCID: https://orcid.org/0009-0000-9791-9619

Natasha.sattarova@yandex.ruhttps://orcid.org/0000-0002-9306-3507ЗинченкоС. В. ZinchenkoS. V. 

 

Зинченко Сергей Викторович – д.м.н., доцент, заведующий кафедрой хирургии ФГАОУ ВО «Казанский (Приволжский) федеральный университет», г. Казань, Российская Федерация

ORCID: https://orcid.org/0000-0002-9306-3507, SPIN: 5381-4389, AuthorID: 905414, Scopus Author ID: 57209135318

 

Sergey V. Zinchenko – Dr. Sci. (Medicine), Associate Professor, Head of the Department of Surgery, Kazan Federal University, Kazan, Russian Federation

ORCID: https://orcid.org/0000-0002-9306-3507, SPIN: 5381-4389, AuthorID: 905414, Scopus Author ID: 57209135318

zinchenkos.v@mail.ruКазанский (Приволжский) федеральный университет; <p> Республиканский клинический онкологический диспансер Министерства здравоохранения Республики Татарстан им. проф. М.З. Сигала <p> г. Казань, Российская ФедерацияKazan Federal University; <p> The Republican Clinical Oncological Dispensary named after Prof. M.Z. Sigal <p> Kazan, Russian FederationМосковский научно-практический центр лабораторных исследований Департамента здравоохранения <p> г. Москва, Российская ФедерацияMoscow Research and Practical Center for Laboratory Diagnostics <p> Moscow, Russian FederationКазанская государственная медицинская академия – филиал ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской Федерации <p> г. Казань, Российская ФедерацияKazan State Medical Academy – Branch Campus of the Russian Medical Academy of Continuous Professional Education<p> Kazan, Russian FederationКазанский (Приволжский) федеральный университет <p> г. Казань, Российская ФедерацияKazan Federal University <p> Kazan, Russian Federation202517122025643645Copyright &#x00A9; Сигал А.М., Гордиев М.Г., Мостюков Б.Ф., Саттарова Н.З., Зинченко С.В., 20252025Сигал А.М., Гордиев М.Г., Мостюков Б.Ф., Саттарова Н.З., Зинченко С.В.Sigal A.M., Gordiev M.G., Mostyukov B.F., Sattarova N.Z.,  Zinchenko 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://www.cancersp.com/jour/article/view/370Цель исследования

Цель исследования. Определить частоту и сочетание с основными соматическими драйверами герминальной мутации СHEK2 p.Ile157Thr у пациентов с немелкоклеточным раком легкого (НМРЛ) в Республике Татарстан.

Пациенты и методы

Пациенты и методы. Панельное NGS-секвенирование ключевых онкогенов выполнено в опухолевом материале 151 пациента. Библиографический поиск проводился вручную в Google Scholar, PubMed по сочетаниям «CHEK2 I157T», «p.Ile157Thr», «c.470T>C», «NSCLC», «germline», «NGS» и др.; формулировки уточнялись с помощью искусственного интеллекта при обязательной ручной вери‑ фикации. Статистическую обработку выполняли в SPSS v18.0; для сравнения долей применяли точный критерий Фишера, уровень значимости p < 0,05).

Результаты

Результаты. Вариант p.Ile157Thr выявлен у 12 (7,9 %) пациентов: у 100 % подтверждена гистологически аденокарцинома. Семейный анамнез злокачественных опухолей зафиксирован у 2 (16,7 %) пациентов, множественные первичные новообразования – у 2 (16,7 %). Сопутствующие драйверные мутации обнаружены у 8 (66,7 %): EGFR – у 5 (62,5 %), у 3 (37,5 %) была обнаружена одна из мутаций KRAS (12,5 %), NRAS и BRAF соответственно. У 4 (33,3 %) p.Ile157Thr было единственным молекулярным событием. При сравнении носителей и неносителей CHEK2 p.Ile157Thr по стадиям заболевания и частоте сопутствующих драйверов статистически значимых различий не выявлено (точный критерий Фишера, p > 0,05).

Заключение

Заключение. Герминальный вариант CHEK2 p.Ile157Thr (c.470T>C) выявлен у части пациентов с аденокарциномой легкого и в ряде случаев сочетался с соматическими драйверными мутациями. Полученные данные уточняют его частоту в исследуемой популяции и описывают молекулярные особенности опухолей у носителей, что может быть использовано в дальнейших исследованиях кли‑ нического значения CHEK2 при НМРЛ.

Purpose of the study

Purpose of the study. To determine the frequency and co-occurrence with major somatic drivers of the germline CHEK2 p.Ile157Thr mutation in patients with non-small cell lung cancer (NSCLC) in the Republic of Tatarstan.

Patients and methods

Patients and methods. Targeted next-generation sequencing (NGS) of key oncogenes was performed on tumor tissue from 151 patients. A bibliographic search was carried out manually in Google Scholar and PubMed using the terms “CHEK2 I157T,” “p.Ile157Thr,” “c.470T>C,” “NSCLC,” “germline,” “NGS,” among others; search formulations were refined with the aid of artificial intelligence, followed by mandatory manual verification. Statistical analysis was performed in SPSS v18.0. Proportions were compared using Fisher’s exact test with a significance threshold of p < 0.05.

Results

Results. The p.Ile157Thr variant was identified in 12 patients (7.9 %); all cases (100 %) were histologically confirmed adenocarcinomas. A positive family history of malignant tumors was recorded in 2 patients (16.7 %), and multiple primary malignancies in 2 patients (16.7 %). Concomitant driver mutations were detected in 8 patients (66.7 %): EGFR in 5 (62.5 %), while 3 patients (37.5 %) harbored mutations in KRAS (12.5 %), NRAS, and BRAF, respectively. In 4 patients (33.3 %), p.Ile157Thr was the sole molecular event. In a comparison of carriers versus non-carriers of CHEK2 p.Ile157Thr, no statistically significant differences were observed in stage distribution or in the frequency of co-occurring driver alterations (Fisher’s exact test, p > 0.05).

Conclusion

Conclusion. The germline CHEK2 p.Ile157Thr (c.470T>C) variant was identified in a subset of patients with lung adenocarcinoma and in several cases was accompanied by somatic driver mutations. The obtained data refine the frequency of this variant in the studied population and describe the molecular characteristics of tumors in carriers, providing a basis for further evaluation of the potential clinical relevance of CHEK2 in NSCLC.

CHEK2p.Ile157Thrc.470T>CI157Tрак легкогонемелкоклеточный рак легкогоNGScеквенирование нового поколениягерминальные мутациинаследственные мутацииCHEK2p.Ile157Thrc.470T>CI157Tlung cancernon-small cell lung cancerNGSnext-generation sequencinggermline mutationshereditary mutationsReferencesWild CP, Weiderpass E, Stewart BW (eds). World Cancer Report. Lyon (FR): International Agency for Research on Cancer; 2020. Доступно по: https://www.ncbi.nlm.nih.gov/books/NBK606998/Wild CP, Weiderpass E, Stewart BW (eds). World Cancer Report. Lyon (FR): International Agency for Research on Cancer; 2020. Available at: https://www.ncbi.nlm.nih.gov/books/NBK606998/Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature. 2018 Jan 24;553(7689):446–454. https://doi.org/10.1038/nature25183Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature. 2018 Jan 24;553(7689):446–454. https://doi.org/10.1038/nature25183Hecht SS. Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nat Rev Cancer. 2003 Oct;3(10):733-44. https://doi.org/10.1038/nrc1190 Erratum in: Nat Rev Cancer. 2004 Jan;4(1):84.Hecht SS. Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nat Rev Cancer. 2003 Oct;3(10):733-44. https://doi.org/10.1038/nrc1190 Erratum in: Nat Rev Cancer. 2004 Jan;4(1):84.Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004 Jun 4;304(5676):1497–1500. https://doi.org/10.1126/science.1099314Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004 Jun 4;304(5676):1497–1500. https://doi.org/10.1126/science.1099314Kris MG, Johnson BE, Berry LD, Kwiatkowski DJ, Iafrate AJ, Wistuba II, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014 May 21;311(19):1998–2006. https://doi.org/10.1001/jama.2014.3741Kris MG, Johnson BE, Berry LD, Kwiatkowski DJ, Iafrate AJ, Wistuba II, et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014 May 21;311(19):1998–2006. https://doi.org/10.1001/jama.2014.3741Sorscher S, LoPiccolo J, Heald B, Chen E, Bristow SL, Michalski ST, et al. Rate of Pathogenic Germline Variants in Patients With Lung Cancer. JCO Precis Oncol. 2023 Sep;7:e2300190. https://doi.org/10.1200/po.23.00190Sorscher S, LoPiccolo J, Heald B, Chen E, Bristow SL, Michalski ST, et al. Rate of Pathogenic Germline Variants in Patients With Lung Cancer. JCO Precis Oncol. 2023 Sep;7:e2300190. https://doi.org/10.1200/po.23.00190Bell DW, Varley JM, Szydlo TE, Kang DH, Wahrer DC, Shannon KE, et al. Heterozygous germ line hCHK2 mutations in Li-Frau meni syndrome. Science. 1999 Dec 24;286(5449):2528–2531. https://doi.org/10.1126/science.286.5449.2528Bell DW, Varley JM, Szydlo TE, Kang DH, Wahrer DC, Shannon KE, et al. Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science. 1999 Dec 24;286(5449):2528–2531. https://doi.org/10.1126/science.286.5449.2528Meijers-Heijboer H, van den Ouweland A, Klijn J, Wasielewski M, de Snoo A, Oldenburg R, et al.; CHEK2-Breast Cancer Consortium. Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet. 2002 May;31(1):55–59. https://doi.org/10.1038/ng879Meijers-Heijboer H, van den Ouweland A, Klijn J, Wasielewski M, de Snoo A, Oldenburg R, et al.; CHEK2-Breast Cancer Consortium. Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet. 2002 May;31(1):55–59. https://doi.org/10.1038/ng879Vahteristo P, Bartkova J, Eerola H, Syrjäkoski K, Ojala S, Kilpivaara O, et al. A CHEK2 genetic variant contributing to a sub stantial fraction of familial breast cancer. Am J Hum Genet. 2002 Aug;71(2):432–438. https://doi.org/10.1086/341943Vahteristo P, Bartkova J, Eerola H, Syrjäkoski K, Ojala S, Kilpivaara O, et al. A CHEK2 genetic variant contributing to a substantial fraction of familial breast cancer. Am J Hum Genet. 2002 Aug;71(2):432–438. https://doi.org/10.1086/341943Kilpivaara O, Vahteristo P, Falck J, Syrjäkoski K, Eerola H, Easton D, et al. CHEK2 variant I157T may be associated with in creased breast cancer risk. Int J Cancer. 2004 Sep 10;111(4):543–547. https://doi.org/10.1002/ijc.20299Kilpivaara O, Vahteristo P, Falck J, Syrjäkoski K, Eerola H, Easton D, et al. CHEK2 variant I157T may be associated with increased breast cancer risk. Int J Cancer. 2004 Sep 10;111(4):543–547. https://doi.org/10.1002/ijc.20299Cybulski C, Górski B, Huzarski T, Masojć B, Mierzejewski M, Debniak T, et al. CHEK2 is a multiorgan cancer susceptibility gene. Am J Hum Genet. 2004 Dec;75(6):1131–1135. https://doi.org/10.1086/426403Cybulski C, Górski B, Huzarski T, Masojć B, Mierzejewski M, Debniak T, et al. CHEK2 is a multiorgan cancer susceptibility gene. Am J Hum Genet. 2004 Dec;75(6):1131–1135. https://doi.org/10.1086/426403Weischer M, Bojesen SE, Ellervik C, Tybjaerg-Hansen A, Nordestgaard BG. CHEK2*1100delC genotyping for clinical as sessment of breast cancer risk: meta-analyses of 26,000 patient cases and 27,000 controls. J Clin Oncol. 2008 Feb 1;26(4):542–548. https://doi.org/10.1200/jco.2007.12.5922Weischer M, Bojesen SE, Ellervik C, Tybjaerg-Hansen A, Nordestgaard BG. CHEK2*1100delC genotyping for clinical assessment of breast cancer risk: meta-analyses of 26,000 patient cases and 27,000 controls. J Clin Oncol. 2008 Feb 1;26(4):542–548. https://doi.org/10.1200/jco.2007.12.5922Xiang HP, Geng XP, Ge WW, Li H. Meta-analysis of CHEK2 1100delC variant and colorectal cancer susceptibility. Eur J Can cer. 2011 Nov;47(17):2546–2551. https://doi.org/10.1016/j.ejca.2011.03.025Xiang HP, Geng XP, Ge WW, Li H. Meta-analysis of CHEK2 1100delC variant and colorectal cancer susceptibility. Eur J Cancer. 2011 Nov;47(17):2546–2551. https://doi.org/10.1016/j.ejca.2011.03.025Stolarova L, Kleiblova P, Janatova M, Soukupova J, Zemankova P, Macurek L, Kleibl Z. CHEK2 Germline Variants in Cancer Predisposition: Stalemate Rather than Checkmate. Cells. 2020 Dec 12;9(12):2675. https://doi.org/10.3390/cells9122675Stolarova L, Kleiblova P, Janatova M, Soukupova J, Zemankova P, Macurek L, Kleibl Z. CHEK2 Germline Variants in Cancer Predisposition: Stalemate Rather than Checkmate. Cells. 2020 Dec 12;9(12):2675. https://doi.org/10.3390/cells9122675Бермишева М. А., Тахирова З. Р., Богданова Н., Хуснутдинова Э. К. Частота мутаций в гене CHEK2 у больных раком молочной железы из Республики Башкортостан. Молекулярная биология. 2014;48(1):55–61. https://doi.org/10.7868/s0026898414010029Bermisheva MA, Takhirova ZR, Khusnutdinova EK, Bogdanova N. Frequency of CHEK2 gene mutations in breast cancer patients from republic of Bashkortostan. Molecular Biology. 2014;48(1):46–51. https://doi.org/10.7868/s0026898414010029Казаков А. М., Лактионов К. К., Саранцева К. А., Гордиев М. Г. Результаты таргетного секвенирования немелкокле точного рака легкого I–IIIA стадий и их связь с клинико морфологическими параметрами опухоли. Российский биотерапевтический журнал. 2023;24(3):291–299. https://doi.org/10.31917/2403291Kazakov AM, Laktionov KK, Sarantseva KA, Gordiev MG. Relationship between molecular genetic and clinical and morphological parameters in patients with stage I–IIIA non-small cell lung cancer. Russian Journal of Biotherapy. 2023;24(3):291–299. (In Russ.). https://doi.org/10.31917/2403291Brennan P, McKay J, Moore L, Zaridze D, Mukeria A, Szeszenia-Dabrowska N, et al. Uncommon CHEK2 mis-sense variant and reduced risk of tobacco-related cancers: case control study. Hum Mol Genet. 2007 Aug 1;16(15):1794–1801. https://doi.org/10.1093/hmg/ddm127Brennan P, McKay J, Moore L, Zaridze D, Mukeria A, Szeszenia-Dabrowska N, et al. Uncommon CHEK2 mis-sense variant and reduced risk of tobacco-related cancers: case control study. Hum Mol Genet. 2007 Aug 1;16(15):1794–1801. https://doi.org/10.1093/hmg/ddm127Cybulski C, Masojc B, Oszutowska D, Jaworowska E, Grodzki T, Waloszczyk P, et al. Constitutional CHEK2 mutations are associated with a decreased risk of lung and laryngeal cancers. Carcinogenesis. 2008 Apr;29(4):762–765. https://doi.org/10.1093/carcin/bgn044Cybulski C, Masojc B, Oszutowska D, Jaworowska E, Grodzki T, Waloszczyk P, et al. Constitutional CHEK2 mutations are associated with a decreased risk of lung and laryngeal cancers. Carcinogenesis. 2008 Apr;29(4):762–765. https://doi.org/10.1093/carcin/bgn044Wang Y, McKay JD, Rafnar T, Wang Z, Timofeeva MN, Broderick P, et al. Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer. Nat Genet. 2014 Jul;46(7):736-41. https://doi.org/10.1038/ng.3002 Epub 2014 Jun 1. Erratum in: Nat Genet. 2017 Mar 30;49(4):651. https://doi.org/10.1038/ng0417-651aWang Y, McKay JD, Rafnar T, Wang Z, Timofeeva MN, Broderick P, et al. Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer. Nat Genet. 2014 Jul;46(7):736-41. https://doi.org/10.1038/ng.3002 Epub 2014 Jun 1. Erratum in: Nat Genet. 2017 Mar 30;49(4):651. https://doi.org/10.1038/ng0417-651aХарагезов Д. А., Лазутин Ю. Н., Мирзоян Э. А., Милакин А. Г., Статешный О. Н., Лейман И. А., и др. Молекулярные мишени немелколеточного рака легкого (НМРЛ) вне «главной тройки». Южно-Российский онкологический жур нал. 2021;2(4):38–47. https://doi.org/10.37748/2686-9039-2021-2-4-5Kharagezov DA, Lazutin YuN, Mirzoyan EA, Milakin AG, Stateshny ON, Leiman IA, Chubaryan AV, Iozefi KD. Molecular targets of non-small cell lung cancer outside the "top three". South Russian Journal of Cancer. 2021;2(4):38–47. https://doi.org/10.37748/2686-9039-2021-2-4-5Zhang SS, Lee JK, Tukachinsky H, Schrock AB, Nagasaka M, Ou SI. A High Percentage of NSCLC With Germline CHEK2 Mutation Harbors Actionable Driver Alterations: Survey of a Cancer Genomic Database and Review of Literature. JTO Clin Res Rep. 2022 Aug 6;3(9):100387. https://doi.org/10.1016/j.jtocrr.2022.100387Zhang SS, Lee JK, Tukachinsky H, Schrock AB, Nagasaka M, Ou SI. A High Percentage of NSCLC With Germline CHEK2 Mutation Harbors Actionable Driver Alterations: Survey of a Cancer Genomic Database and Review of Literature. JTO Clin Res Rep. 2022 Aug 6;3(9):100387. https://doi.org/10.1016/j.jtocrr.2022.100387Mezquita L, Kuang Z, Sivakumar S, Sokol ES, Laguna JC, Pastor B. et al. Pathogenic Germline Variants in Patients with NonSmall Cell Lung Cancer (NSCLC) Detected by Tissue Comprehensive Genomic Profiling. Journal of Thoracic Oncology. 2023;18(S11):151. https://doi.org/10.1016/j.jtho.2023.09.217Mezquita L, Kuang Z, Sivakumar S, Sokol ES, Laguna JC, Pastor B. et al. Pathogenic Germline Variants in Patients with Non-Small Cell Lung Cancer (NSCLC) Detected by Tissue Comprehensive Genomic Profiling. Journal of Thoracic Oncology. 2023;18(S11):151. https://doi.org/10.1016/j.jtho.2023.09.217Zhou N, Xu Y, Huang Y, Ye G, Luo L, Song Z. Comprehensive genomic profiling of Chinese lung cancer characterizes germ line-somatic mutation interactions influencing cancer risk. J Transl Med. 2025 Feb 18;23(1):199. https://doi.org/10.1186/s12967-025-06096-zZhou N, Xu Y, Huang Y, Ye G, Luo L, Song Z. Comprehensive genomic profiling of Chinese lung cancer characterizes germline-somatic mutation interactions influencing cancer risk. J Transl Med. 2025 Feb 18;23(1):199. https://doi.org/10.1186/s12967-025-06096-zDaly MB, Pal T, AlHilli Z, Arun B, Buys SS, Cheng HH, et al. NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment – Breast, Ovarian, Pancreatic & Prostate; Version 3.2025. Plymouth Meeting (PA): National Com prehensive Cancer Network; 6 Mar 2025 [Дата обращения: 23 июня 2025 года]. Доступно по: https://www.nccn.org/professionals/physician_gls/pdf/genetics_bopp.pdfDaly MB, Pal T, AlHilli Z, Arun B, Buys SS, Cheng HH, et al. NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment – Breast, Ovarian, Pancreatic & Prostate; Version 3.2025. Plymouth Meeting (PA): National Comprehensive Cancer Network; 6 Mar 2025 [Дата обращения: 23 июня 2025 года]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/genetics_bopp.pdfGupta S, Weiss JM, Axell L, Burke CA, Chen LM, Chung DC, et al. NCCN Clinical Practice Guidelines in Oncology: Genetic/ Familial High-Risk Assessment – Colorectal, Endometrial & Gastric; Version 1.2025. Plymouth Meeting (PA): National Com prehensive Cancer Network; 13 Jun 2025 [Дата обращения: 23 июня 2025 года]. Доступно по: https://www.nccn.org/professionals/physician_gls/pdf/genetics_ceg.pdfGupta S, Weiss JM, Axell L, Burke CA, Chen LM, Chung DC, et al. NCCN Clinical Practice Guidelines in Oncology: Genetic/ Familial High-Risk Assessment – Colorectal, Endometrial & Gastric; Version 1.2025. Plymouth Meeting (PA): National Comprehensive Cancer Network; 13 Jun 2025 [Accessed 23 June 2025]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/genetics_ceg.pdfWood DE, Kazerooni EA, Aberle DR, Baines J, Boer B, Brown LM, et al. NCCN Clinical Practice Guidelines in Oncology: Lung Cancer Screening; Version 1.2025. Plymouth Meeting (PA): National Comprehensive Cancer Network; 14 Oct 2024 [Дата обращения: 23 июня 2025 года]. Доступно по: https://www.nccn.org/professionals/physician_gls/pdf/lung_screening.pdfWood DE, Kazerooni EA, Aberle DR, Baines J, Boer B, Brown LM, et al. NCCN Clinical Practice Guidelines in Oncology: Lung Cancer Screening; Version 1.2025. Plymouth Meeting (PA): National Comprehensive Cancer Network; 14 Oct 2024 [Accessed 23 June 2025]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/lung_screening.pdfRiely GJ, Wood DE, Aisner DL, Axtell AL, Bauman JR, Bharat A, et al. NCCN Clinical Practice Guidelines in Oncology: NonSmall Cell Lung Cancer; Version 5.2025. Plymouth Meeting (PA): National Comprehensive Cancer Network; 20 Jun 2025 [Дата обращения: 23 июня 2025 года]. Доступно по: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf.Riely GJ, Wood DE, Aisner DL, Axtell AL, Bauman JR, Bharat A, et al. NCCN Clinical Practice Guidelines in Oncology: NonSmall Cell Lung Cancer; Version 5.2025. Plymouth Meeting (PA): National Comprehensive Cancer Network; 20 Jun 2025 [Accessed 23 June 2025]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf.

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