Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC14210.15690/vramn.v68i9.772MOLECULAR MEDICINE AND GENETICS: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ ГЕНЕТИКИ И МОЛЕКУЛЯРНОЙ МЕДИЦИНЫSTRUCTURAL AND FUNCTIONAL ANALYSIS OF TUMOR GENOMES AND THE DEVELOPMENT OF TEST SYSTEMS FOR EARLY DIAGNOSIS, PROGNOSIS AND CANCER THERAPY OPTIMIZATIONСТРУКТУРНО-ФУНКЦИОНАЛЬНЫЙ АНАЛИЗ ОПУХОЛЕВЫХ ГЕНОМОВ И РАЗРАБОТКА ТЕСТ-СИСТЕМ ДЛЯ РАННЕЙ ДИАГНОСТИКИ, ПРОГНОЗА ТЕЧЕНИЯ И ОПТИМИЗАЦИИ ТЕРАПИИ ЗЛОКАЧЕСТВЕННЫХ НОВООБРАЗОВАНИЙZaletaevD. V.ЗалетаевД. В.
Russian Federation

PhD, professor, Head of the epigenetics laboratory of the Federal State Budgetary Institution «Scientific Research Center of Medical Genetics» of RAMS, Head of the laboratory of human molecular genetics of I.M. Sechenov First Moscow State Medical University Address: 1, Moskvorechye St., Moscow, 115478, tel.: (985) 991-64-46

zalnem@mail.ruStrel'nikovV. V.СтрельниковВ. В.
Russian Federation

PhD, assistant professor, leading scientist of the epigenetics laboratory of the Federal State Budgetary Institution «Scientific Research Center of Medical Genetics» of the RAMS Address: Moskvorechye St., 1, Moscow, 115478, tel.: (495) 622-96-35

vstrel@list.ruNemtsovaM. V.НемцоваМ. В.
Russian Federation

a, PhD, professor, leading scientist of the laboratory of human molecular genetics of the Statefunded Educational Institution of Higher Professional Education «I.M. Sechenov First Moscow State Medical University» Address: Trubetskaya St., 8, build. 2, Moscow, 119991, tel.: (495) 622-96-35

nemtsova_m_v@mail.ruBabenkoO. V.БабенкоО. В.
Russian Federation

MD, leading scientist of the epigenetics laboratory of the Federal State Budgetary Institution «Scientific Research Center of Medical Genetics» of the RAMS Address: Moskvorechye St., 1, Moscow, 115478, tel.: (495) 622-96-35

polyakk@list.ruKuznetsovaE. B.КузнецоваЕ. Б.
Russian Federation

MD, senior scientist of the epigenetics laboratory of the Federal State Budgetary Institution «Scientific Research Center of Medical Genetics» of the RAMS, leading scientist of the laboratory of human molecular genetics of I.M. Sechenov First Moscow State Medical University Address: Moskvorechye St., 1, Moscow, 115478, tel.: (495) 622-96-35

kuznetsova.k@bk.ruZemlyakovaV. V.ЗемляковаВ. В.
Russian Federation

MD, senior scientist of the epigenetics laboratory of the Federal State Budgetary Institution «Scientific Research Center of Medical Genetics» of the RAMS, senior scientist of the laboratory of human molecular genetics of I.M. Sechenov First Moscow State Medical University, The Ministry of Health of the Russian Federation Address: Moskvorechye St., 1, Moscow, 115478, tel.: (495) 622-96-35

valzem@inbox.ruKekeevaT. V.КекееваТ. В.
Russian Federation

MD, research scientist of the laboratory of human molecular genetics of I.M. Sechenov First Moscow State Medical University, The Ministry of Health of the Russian Federation Address: Trubetskaya St., 8, build. 2, Moscow, 119991, tel.: (495) 622-96-35

kekeeva@mail.ruMikhailenkoD. S.МихайленкоД. С.
Russian Federation

MD, senior scientist of the epigenetics laboratory of the Federal State Budgetary Institution «Scientific Research Center of Medical Genetics» of the RAMS Address: Moskvorechye St., 1, Moscow, 115478, tel.: (495) 622-96-35

dimserg@mail.ruTanasA. S.ТанасА. С.
Russian Federation

MD, research scientist of the epigenetics laboratory of the Federal State Budgetary Institution «Scientific Research Center of Medical Genetics» of RAMS Address: Moskvorechye St., 1, Moscow, 115478, tel.: (495) 622-96-35

tanas80@gmail.comRudenkoV. V.РуденкоВ. В.
Russian Federation

PhD in biological sciences, research scientist of the epigenetics laboratory of the Federal State Budgetary Institution «Scientific Research Center of Medical Genetics» of the RAMS Address: Moskvorechye St., 1, Moscow, 115478, tel.: (495) 622-96-35

shkarupo@mail.ruBabayanA. Yu.БабаянА. Ю.
Russian Federation

research scientist of the epigenetics laboratory of the Federal State Budgetary Institution «Scientific Research Center of Medical Genetics» of the RAMS Address: Moskvorechye St., 1, Moscow, 115478, tel.: (495) 622-96-35

babayan-a@inbox.ruAlekseevaE. A.АлексееваЕ. А.
Russian Federation

research scientist of the epigenetics laboratory of the Federal State Budgetary Institution «Scientific Research Center of Medical Genetics» of the RAMS Address: Moskvorechye St., 1, Moscow, 115478, tel.: (495) 622-96-35

katrina_5@inbox.ruSimonovaO. A.СимоноваО. А.
Russian Federation

research scientist of the epigenetics laboratory of the Federal State Budgetary Institution «Scientific Research Center of Medical Genetics» of the RAMS Address: Moskvorechye St., 1, Moscow, 115478, tel.: (495) 622-96-35

simonova_o.a@mail.ruResearch Centre for Medical Genetics of Russian Academy of Medical Sciences, Moscow, Russian Federation I.M. Sechenov First Moscow State Medical University, Russian FederationМедико-генетический научный центр РАМН, Москва, Российская Федерация Первый Московский государственный медицинский университет им. И.М. Сеченова, Российская ФедерацияResearch Centre for Medical Genetics of Russian Academy of Medical Sciences, Moscow, Russian FederationМедико-генетический научный центр РАМН, Москва, Российская ФедерацияI.M. Sechenov First Moscow State Medical University, Russian FederationПервый Московский государственный медицинский университет им. И.М. Сеченова, Российская ФедерацияResearch Centre for Medical Genetics of Russian Academy of Medical Sciences, Moscow, Russian FederationПервый Московский государственный медицинский университет им. И.М. Сеченова, Российская Федерация10092013689Vestnik Rossiiskoi akademii medetsinskikh nauk / Annals of the Russian academy of medical sciencesВестник Российской академии медицинских наук71407082015Copyright ©; 1970, "Paediatrician" Publishers LLCCopyright ©; 1970, Издательство "Педиатръ"1970"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/142

The article discusses results of the structural and functional analysis of molecular genetic abnormalities in various malignant tumors. Investigations have discovered more than 20 new markers for sporadic breast cancer. Several of them formed the test system, allowing the diagnosis with a specificity of 100%. Appearance of TMPRSS2/ERG4 chimeric gene is a frequent tumor-specific event, its expression is correlated with more aggressive forms of prostate cancer, may serve as a molecular marker for tumor cells and androgen assessment of tumor response to hormonal therapy. The effective systems for the early diagnosis of cervix and endometrium cancer were developed as well. Mutations in the VHL, deletions of chromosome 3 and methylation of several genes can predict the course and selection of effective therapy of clear cell kidney cancer. a number of molecular markers were identified for early diagnosis and prognosis of recurrence of bladder cancer. For diagnosis, prognosis and treatment of brain tumors we developed an effective complex system of markers. Protocol of molecular genetics investigation reveals the cause of the disease by more than 90% of patients with retinoblastoma. In order to study abnormal methylation in tumor genomes an innovative technology AFLOAT has been developed that allows to efficiently identify new markers with diagnostic value. Test systems of molecular genetic and epigenetic markers for early diagnosis and prognosis as well as for cancer therapy optimization have shown to be effective, have been approved for use in clinical practice and are being introduced into practical healthcare.

Рассматриваются результаты структурно-функционального анализа молекулярно-генетических нарушений при различных злокачественных опухолях. Исследования позволили обнаружить более 20 новых маркеров для спорадического рака молочной железы, из которых сформированы тест-системы, позволяющие проводить диагностику со специфичностью 100%. Образование химерного гена TMPRSS2/ERG4 является частым опухоль-специфическим событием, его экспрессия коррелирует с более агрессивными формами рака предстательной железы может служить молекулярным маркером андрогенчувствительности опухолевых клеток и оценки ответа опухоли на гормональную терапию. Разработаны эффективные системы для ранней диагностики рака шейки матки и эндометрия. Мутации гена VHL, делеции хромосомы 3 и метилирование ряда генов позволяет прогнозировать течение и подбор эффективной терапии светлоклеточного рака почки. Для ранней диагностики, прогноза течения и рецидивирования рака мочевого пузыря определен целый ряд молекулярных маркеров. Для диагностики, прогноза и лечения опухолей мозга разработана эффективная комплексная система маркеров. Протокол молекулярно-генетического исследования позволяет обнаружить причину заболевания более чем у 90% пациентов с ретинобластомой. Для исследования аномального метилирования в опухолевых геномах разработана инновационная технология AFLOAT, позволяющая эффективно выявлять новые маркеры, имеющие диагностическое значение. Тест-системы молекулярно-генетических и эпигенетических маркеров для ранней диагностики, прогноза течения и оптимизации терапии злокачественных новообразований показали свою эффективность, получили разрешение на использование в клинической практике и в настоящее время активно внедряются в практическое здравоохранение.

malignant tumorsmolecular genetic markersabnormal methylationDNA diagnosticstest-systemsзлокачественные новообразованиямолекулярно-генетические маркерыаномальное метилированиеДНК-диагностикатест-системы1. Strategii razvitiya meditsinskoy nauki v Rossiyskoy Federatsii na period do 2025 goda. Rasporyazhenie Pravitel'stva RF ot 28.12.2012 № 2580-r [The Strategy for the Development of Medical Science in the Russian Federation for the Period up to 2025. Edict of the Russian Federation Government dated Dec 28, 2012 No. 2580-р].2. Tanas A.S., Shkarupo V.V., Kuznetsova E.B., Zaletayev D.V., Strelnikov V.V. Novel tools for unbiased DNA differential methylation screening. Epigenomics. 2010; 2 (2): 325–333.3. Rudenko V.V., Tanas A.S., Strelnikov V.V., Kuznetsova E.B., Zaletaev D.V. Skrining anomalnogo metilirovaniya DNK na osnove metoda amplificatsii intermetilirovannykh saytov dlya diagnostiki zlokachestvennogo opukholevogo protsessa. Novaya meditsinskaya DNK-tekhnologiya. Razreshenie FS № 2011/132 ot 27.05.2011 g [Screening of an Abnormal DNA Methylation on the Basis of Amplification Method of the Inter-methylated Sites for a Diagnosis of Cancerous Neoplastic Process. New medical DNA Technology. Federal Service permit No. 2011/132 dated May 27, 2011]. Мoscow, 2011.4. Rudenko V.V., Tanas A.S., Kuznetsova E.B., Strelnikov V.V., Zaletaev D.V. Sposob formirovaniya paneley markerov metilirovaniya DNK. [Forming Method of the Panels of Markers of the DNA Methylation. Invention Patent No. 2472859, priority May 18, 2011]. Мoscow, 2011.5. Kuznetsova E.B., Kekeeva T.V., Larin S.S., Zemliakova V.V., Babenko O.V., Nemtsova M.V., Zaletaev D.V., Strelnikov V.V. Mol. Biol. (Moskva). 2007; 41 (4): 624–633.6. Kuznetsova E.B., Kekeeva T.V., Larin S.S., Zemlyakova V.V., Khomyakova A.V., Babenko O.V., Nemtsova M.V., Zaletayev D.V., Strelnikov V.V. J. Carcinogen. 2007; 6: 9.7. Rudenko V.V., Tanas A.S., Strelnikov V.V. 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