Molecular BiologyMolecular BiologyМолекулярная биология0026-89843034-5553The Russian Academy of Sciences69968110.7868/S3034555325060091МОЛЕКУЛЯРНАЯ БИОЛОГИЯ КЛЕТКИResearch ArticleMolecular and Genetic Analysis of a Rare Primary Culture of Head and Neck ParagangliomaМОЛЕКУЛЯРНО-ГЕНЕТИЧЕСКИЙ АНАЛИЗ РЕДКОЙ ПЕРВИЧНОЙ КУЛЬТУРЫ ПАРАГАНГЛИОМЫ ГОЛОВЫ И ШЕИSnezhkinaA. VСнежкинаА. Вleftger@rambler.ruFedorovaM. SФедороваМ. Сemail@example.comPavlovV. SПавловВ. Сemail@example.comPudovaE. AПудоваЕ. Аemail@example.comKatuninaI. VКатунинаИ. Вemail@example.comKalininD. VКалининД. Вemail@example.comKobelyatskayaA. AКобеляцкаяА. Аemail@example.comKudryavtsevaA. VКудрявцеваА. Вemail@example.comEngelhardt Institute of Molecular Biology, Russian Academy of SciencesИнститут молекулярной биологии им. В.А. Энгельгардта Российской академии наукVishnevsky Institute of Surgery, Ministry of Health of the Russian FederationНациональный медицинский исследовательский центр хирургии им. А.В. Вишневского Министерства здравоохранения Российской Федерации25122025596VOL 59, NO6 (2025)ТОМ 59, №6 (2025)988100127122025Copyright ©; 2025, Russian Academy of SciencesCopyright ©; 2025, Российская академия наук2025Russian Academy of SciencesРоссийская академия наукhttps://vietnamjournal.ru/0026-8984/article/view/699681

Head and neck paragangliomas (HNPGLs) are rare neuroendocrine tumors that originate in the parasympathetic paraganglia of the head and neck. The diagnosis of these tumors is challenging, and the therapeutic options are limited. The study of HNPGLs is fraught with challenges at every stage. One of the main problems is the absence of HNPGL cell lines in cell repositories, which is associated with the difficulty of their culturing and low division rate. In this regard, neither functional nor preclinical studies are available for this category of tumors. This significantly slows down the study of the molecular mechanisms of HNPGL pathogenesis and the development of effective therapeutic approaches. Here, we investigated the molecular genetic characteristics of the primary HNPGL culture were. Using the single-cell RNA sequencing method, expression patterns were analyzed, and cell types were annotated. The results demonstrated that the HNPGL primary culture cells were optimally divided into three clusters, had different degrees of differentiation, expressing neural tissue cell and stem cell markers. Exome sequencing revealed genetic abnormalities in the HNPGL culture, including mutations in the IGSF3, DHH, EXOSC8, SERPINA1, TYR and NQO1 genes, aneuploidy, as well as multiple chromosomal duplications and deletions. These results enhance our knowledge of the molecular genetic features of successfully cultured HNPGL tumor cells.

Параганглиомы головы и шеи (ПГШ) – это редкие нейроэндокринные опухоли человека, которые развиваются из парасимпатических параганглиев головы и шеи. Диагностика этих опухолей затруднена, а методы лечения ограничены. Изучение ПГШ сопряжено с трудностями на разных этапах исследования. Одна из основных проблем – отсутствие в клеточных репозиториях клеточных линий ПГШ, что связано со сложностью их культивирования и медленной скоростью деления. В связи с этим для этой категории опухолей недоступны ни функциональные, ни доклинические исследования, что сильно замедляет прогресс в изучении молекулярных механизмов развития заболевания и разработки эффективных способов терапии. Мы провели анализ молекулярно-генетических характеристик первичной культуры ПГШ. С использованием метода секвенирования РНК единичных клеток выполнен анализ паттернов экспрессии и аннотация типов клеток. Показано, что клетки первичной культуры ПГШ оптимально разделяются на три кластера, имеют разную степень дифференцировки и экспрессируют маркеры клеток нервной ткани и маркеры стволовости. Методом секвенирования экзома выявлены генетические нарушения в культуре ПГШ: мутации генов IGSF3, DHH, EXOSC8, SERPINA1, TYR и NQO1, анеуплоидия, множественные дупликации всех хромосом и делеции хромосом 1, 3, 7, 11, 15, 21, 22 и X. Полученные результаты расширяют наши знания о молекулярно-генетических особенностях успешно культивируемых опухолевых клеток ПГШ.

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