medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.1234/XXXX-XXXX-2016-6-25-30medgen-139Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHАнализ клинического экзома рака желудкаClinical exome sequencing of gastric cancerКекееваТ. В.KekeevaT. V.kekeeva@mail.ruХашимовЛ. Х.KhashimovL. Kh.noemail@neicon.ruЛядовВ. К.LyadovV. K.noemail@neicon.ruКаныгинаА. В.KanyginaA. V.noemail@neicon.ruАндрееваЮ. Ю.AndreevaYu. Yu.noemail@neicon.ruЗавалишинаЛ. Э.ZavalishinaL. E.noemail@neicon.ruПоддубнаяИ. В.PoddubnayaI. V.noemail@neicon.ruСтрельниковВ. В.StrelnikovV. V.noemail@neicon.ruЗалетаевД. В.ZaletaevD. V.noemail@neicon.ruФранкГ. А.FrankG. A.noemail@neicon.ruГБОУ ДПО «Российская медицинская академия последипломного образования»Russian FederationФГОУ ВПО «Московский физико-технический институт (государственный университет)»Russian FederationФГБНУ «Медико-генетический научный центр»Russian FederationФГБНУ «Медико-генетический научный центр»; ГБОУ ВПО Первый МГМУ им. И.М. Сеченова Минздрава РоссииRussian Federation2016071020161562530Copyright © Кекеева Т.В., Хашимов Л.Х., Лядов В.К., Каныгина А.В., Андреева Ю.Ю., Завалишина Л.Э., Поддубная И.В., Стрельников В.В., Залетаев Д.В., Франк Г.А., 20162016Кекеева Т.В., Хашимов Л.Х., Лядов В.К., Каныгина А.В., Андреева Ю.Ю., Завалишина Л.Э., Поддубная И.В., Стрельников В.В., Залетаев Д.В., Франк Г.А.Kekeeva T.V., Khashimov L.K., Lyadov V.K., Kanygina A.V., Andreeva Y.Y., Zavalishina L.E., Poddubnaya I.V., Strelnikov V.V., Zaletaev D.V., Frank G.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/139

Идентификация соматических генетических изменений в опухолях несет потенциальную диагностическую и прогностическую информацию о драйверных мутациях и сведения, позволяющие более обоснованно выбрать схему химиотерапевтического лечения для пациентов. Секвенирование клинического экзома уже зарекомендовало себя как высокоэффективный метод поиска мутаций. Проведен анализ соматических опухолевых изменений в клиническом экзоме, включающем 4813 генов, у шести пациентов с раком желудка (РЖ). Двухконцевое секвенирование парных образцов опухоли и нормальной ткани выполнено на приборе Nextseq500 набором «TruSight One Sequencing Panel» (Illumina). Обнаружены 102 различные соматические мутации, все они являлись однонуклеотидными заменами, их них 30 - синонимичными заменами, 66 - несинонимичными и 6 - нонсенс-мутациями. Проанализировано 82 новых мутации, из них 10 мутаций локализованы в генах, участвующих в патогенезе РЖ. Соматическая мутация известной клинической значимости обнаружена у одного пациента, и предположительно драйверные мутации найдены у трех пациентов. Дальнейшие функциональные исследования с последующим длительным наблюдением за пациентами позволят установить значимость найденных мутаций.

The identification of somatic mutations has the potential to offer diagnostic and prognostic information and inform the selection of therapies. The present study is focusing on implementation of clinical exome sequencing using a Trusight one sequencing panel targeted 4,813 genes associated with known clinical phenotypes. Paired-ended sequencing was performed in six gastric cancer samples and six corresponding adjacent normal gastric specimens using Trusight one sequencing panel on a NEXTSEQ500 platform. We found 102 somatic mutations, all of them were SNP, 30 of them were synonymous substitutions, 66 were nonsynonymous substitutions and six were nonsense mutations. We found 82 novel mutations, from them 10 mutations were localized in genes previously associated with gastric cancer pathogenesis. Somatic mutation of established clinical utility was identified for one patient, and predictively driver mutations were found for three patients. Strategies to effectively and responsibly use these diverse results are required to incorporate tumor exome sequencing and other NGS tests into clinical practice.

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