Актуальность

ssmu

Бюллетень сибирской медицины

Bulletin of Siberian Medicine

1682-03631819-3684

Siberian State Medical University, the Ministry of Healthcare of the Russian Federation

10.20538/1682-0363-2020-3-177-187

ssmu-3002

Research Article

ОБЗОРЫ И ЛЕКЦИИ

REVIEW AND LECTURES

Молекулярно-биологические особенности анапластических астроцитом и выделение молекулярных подгрупп их IDH1-мутантных форм с помощью анализа in silico

Molecular characteristics of anaplastic astrocytomas and isolation of molecular subgroups of their IDH1 mutant forms using in silico analysis

https://orcid.org/0000-0003-3223-4584

Никитин

П. В.

Nikitin

P. V.

науч. сотрудник, лаборатория нейроморфологии и молекулярных методов исследования

Россия, 125047, г. Москва, 4-я Тверская-Ямская ул., 16

nikitinpaulv@yandex.com

https://orcid.org/0000-0002-2337-6495

Беляев

А. Ю.

Belyaev

A. Yu.

канд. мед. наук, врач-нейрохирург, лаборатория нейроморфологии и молекулярных методов исследования

Россия, 125047, г. Москва, 4-я Тверская-Ямская ул., 16

https://orcid.org/0000-0001-7206-6365

Рыжова

М. В.

Ryzhov

M. V.

д-р мед. наук, профессор, зав. лабораторией нейроморфологии и молекулярных методовисследования

Россия, 125047, г. Москва, 4-я Тверская-Ямская ул., 16

Национальный медицинский исследовательский центр (НМИЦ) нейрохирургии им. акад. Н.Н. БурденкоРоссияBurdenko Neurosurgical InstituteRussian Federation

2020

07102020

193177187

2020

Никитин П.В., Беляев А.Ю., Рыжова М.В.

Nikitin P.V., Belyaev A.Y., Ryzhov M.V.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://bulletin.ssmu.ru/jour/article/view/3002

Актуальность

Актуальность. Проблема анапластических астроцитом достаточно актуальна в наши дни. В классификации Всемирной организации здравоохранения выделяются анапластическая астроцитома с мутацией в генах IDH1 и IDH2, анапластическая астроцитома без мутаций в генах IDH1 и IDH2, анапластическая астроцитома без дополнительного генетического уточнения.

Целью данной работы стало кластерирование анапластических астроцитом с мутацией в гене IDH1 на основе их цитогенетического профиля для выделения прогностически значимых молекулярных подгрупп, которые могут иметь как клинико-практическое, так и фундаментально-научное значение. Проведен кластерный анализ анапластических астроцитом по их цитогенетическим профилям на основе доступных генетических баз данных опухолей и крупных когортных исследований, а также сравнение кривых выживаемости Каплана – Мейера для различных молекулярных подгрупп пациентов.

Результаты

Результаты. Нам удалось изучить основные генетические особенности межопухолевой гетерогенности анапластических астроцитом и выделить на основе цитогенетического профиля семь молекулярных подгрупп – эмбриональноподобную, инфламмоподобную, делеционную, матриксную, циклиновую, GATA3-зависимую и тирозинкиназную. При этом каждая из этих подгрупп имеет не только отличительные молекулярные характеристики, но и важные клинические особенности.

Заключение

Заключение. Детальное изучение молекулярных свойств анапластических астроцитом позволит не только оптимизировать процесс прогнозирования исходов лечения, но и создать инновационные форматы для таргетной терапии в рамках концепции персонализированной медицины.

Aim

Aim. The problem of anaplastic astrocytomas is quite relevant today. The WHO classification distinguishes IDH1/IDH2 mutant anaplastic astrocytomas, anaplastic astrocytomas without IDH1/IDH2 mutations, and anaplastic astrocytomas not otherwise specified. The aim of this work was to cluster IDH1-mutant anaplastic astrocytomas based on their cytogenetic profile to select prognostically significant molecular subgroups, which can have both clinical and fundamental scientific value.

Materials and methods

Materials and methods. In this work, we performed a cluster analysis of anaplastic astrocytomas according to their cytogenetic profiles based on available genetic databases of tumors and large cohort studies, as well as a comparison of Kaplan – Meyer survival curves for various molecular subgroups of patients.

Results

Results. We studied the main genetic features of the inter-tumor heterogeneity of anaplastic astrocytomas and distinguished seven molecular subgroups based on the cytogenetic profile: embryo-like, inflammatory-like, deletion, matrix, cyclin, GATA3-dependent and tyrosine kinase. Moreover, each of these subgroups has not only distinctive molecular characteristics, but also important clinical features.

Conclusion

Conclusion. A detailed study of the molecular properties of anaplastic astrocytomas will not only optimize the process for predicting treatment outcomes, but also create innovative formats for targeted therapy within the framework of the concept of personalized medicine.

анапластическая астроцитомамутация гена IDH1межопухолевая гетерогенность

anaplastic astrocytomaIDH1 mutationinter-tumor heterogeneity

Исследование выполнено при финансовой поддержке РФФИ в рамках научного проекта № 18-29-01034.

The study was funded by RFBR according to the research project No. 18-29-01034.

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