uzspbgmuУчёные записки Первого Санкт-Петербургского государственного медицинского университета имени академика И. П. ПавловаThe Scientific Notes of the Pavlov University1607-41812541-8807Academician I.P. Pavlov First St. Petersburg State Medical University10.24884/1607-4181-2016-23-4-49-53uzspbgmu-297Research ArticleОРИГИНАЛЬНЫЕ РАБОТЫORIGINAL PAPERSМОЛЕКУЛЯРНО-ГЕНЕТИЧЕСКИЕ ИССЛЕДОВАНИЯ ГЛИАЛЬНЫХ ОПУХОЛЕЙ У ДЕТЕЙMolecular genetic studies of glial tumors in childrenСолтанП. С.SoltanP. S.

Руководитель департамента инновационных технологий

Санкт-Петербург, В.О. Большой проспект, д. 68

pavel.soltan@biovitrum.ruМоисеенкоФ. В.MoiseenkoF. V.

к.м.н., старший научный сотрудник лаборатории нанобиотехнологий СПб АУ РАН

194021, Санкт-Петербург, ул. Хлопина, д.8, корпус 3

moiseenkofv@gmail.comОчколясВ. Н.OchkolyasV. N.

Профессор кафедры нейрохирургии

197022, Санкт-Петербург, ул. Л. Толстого, д. 6-8

ovn@ihb.spb.ruСтарцевВ. Ю.StartsevV. Yu.

Профессор кафедры онкологии, детской онкологии и лучевой терапии СПбГПМУ

194100, Санкт-Петербург, Литовская ул., д. 2

doc.urolog@gmail.comООО " БиоВитрум "РоссияLLC “BioVitrum” (68, Bolshoy Prosp. of Vasilievsky Island, 199178, Russia)Russian FederationСПб АУ РАН, Академический университетРоссияSt. Petersburg’s national research academic university of Russian academy of sciences (8/3, Khlopina Str., St. Petersburg, 194021, Russia)Russian FederationФГБОУ ВО ПСПбГМУ им. И.П. Павлова Минздава РоссииRussian FederationAcademician I.P. Pavlov First St. Petersburg State Medical University (6-8, L. Tosltoy Str., St. Petersburg, 197022, Russia)Russian FederationСПбГПМУРоссияSt. Petersburg’s State Pediatric Medical University (2, Lytovskaya Str., St. Petersburg, 194100, Russia)Russian Federation2016301220162344953Copyright © Солтан П.С., Моисеенко Ф.В., Очколяс В.Н., Старцев В.Ю., 20162016Солтан П.С., Моисеенко Ф.В., Очколяс В.Н., Старцев В.Ю.Soltan P.S., Moiseenko F.V., Ochkolyas V.N., Startsev V.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.sci-notes.ru/jour/article/view/297

Глиобластомы у детей представляют собой наиболее частые злокачественные новообразования среди первичных опухолей головного мозга. Несмотря на развитие комплексного лечебного подхода, включающего нейрохирургические, радиотерапевтические и химиотерапевтические методики, общая выживаемость больных с впервые выявленными опухолями остается крайне низкой, не превышая 14 месяцев. При использовании таргетных препаратов, в частности, гефитиниба, в общей популяции больных продемонстрирована низкая клиническая эффективность. Наиболее перспективным в настоящий момент является определение популяции больных, потенциально чувствительных к действию таргетных препаратов, с учетом определения предиктивных молекулярных маркеров. В данной работе определены мутационные изменения в тканях 30 детских глиобластом. Анализ данных, основанный на результатах массспектрометрического секвенирования (OncoCarta v1.0, Sequenom), позволил определить 298 мутаций в 19 генах и идентифицировать 10 мутаций в 9 опухолях (30 %). Изменения выявлены в генах BRAF, CDK, HRAS, EGFR, FGFR, MET и PI3K. Наиболее часто (6/30, 20 % опухолей) мутации выявлены у участников сигнального каскада EGFR. Полученные результаты позволяют говорить о потенциальных возможностях изучения новейших таргетных препаратов, включая ингибиторы BRAF, для лечения больных детского возраста с глиальными опухолями головного мозга.

Glioblastomas are the most frequent malignant neoplasm among primary brain tumors of childhood. Despite the advances in a multimodality treatment approach including neurosurgery, radiotherapy and chemotherapy, the overall survival of such patients remains poor and doesn’t exceed 14 months. The using of targeted agents such as gefitinib in unselected patient populations showed insufficient efficacy. Nowadays, the most perspective approach is a selection of patient populations potentially sensitive to targeted therapy based on predictive markers of response. We performed a comprehensive analysis of the mutational patterns in 30 glioblastomas of children. Data Analysis was based on the new method of mass spectrometry (OncoCarta v1.0, Sequenom) that enabled us to estimate 298 mutations in 19 genes and to identify 10 mutations in 9 tumors (30 %). Mutations were found in BRAF, CDK, HRAS, EGFR, FGFR, MET and PI3K. The most mutated pathway was EGFR – in 20 % of the samples (6/30). The obtained results seem to be very promising in terms of possibilities of using new targeted agents including BRAF inhibitors for treatment of children with glial brain tumors.

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