oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2022-21-6-38-46oncotomsk-2371Research ArticleКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯCLINICAL STUDIESГенетические особенности опухолей невыявленной первичной локализацииGenetic features of cancer of unknown primaryhttps://orcid.org/0000-0002-2633-9884ЩеголеваА. А.SchegolevaA. A.

Щеголева Анастасия Алексеевна, младший научный сотрудник лаборатории биологии опухолевой прогрессии, 

634009, г. Томск, пер. Кооперативный, 5

Anastasia A. Schegoleva, Junior Researcher of the Laboratory of Cancer Progression Biology, 

5, Kooperativny St., 634009, Tomsk

shegolmay@gmail.comhttps://orcid.org/0000-0001-7385-6609ТретьяковаМ. С.TretyakovaM. S.

Третьякова Мария Сергеевна, младший научный сотрудник лаборатории биологии опухолевой прогрессии, 

634009, г. Томск, пер. Кооперативный, 5

Maria S. Tretyakova, Junior Researcher of the Laboratory of Cancer Progression Biology,

5, Kooperativny St., 634009, Tomsk

https://orcid.org/0000-0002-5705-8479ВоробьевР. С.VorobyovR. S.

Воробьев Ростислав Сергеевич, младший научный сотрудник лаборатории биологии опухолевой прогрессии, 

634009, г. Томск, пер. Кооперативный, 5

Rostislav S. Vorobyov, Junior Researcher of the Laboratory of Cancer Progression Biology,

5, Kooperativny St., 634009, Tomsk

https://orcid.org/0000-0001-8002-3189АнанинаО. А.AnaninaO. A.

Ананина Ольга Александровна, кандидат медицинских наук, старший научный сотрудник лаборатории эпидемиологии,

634009, г. Томск, пер. Кооперативный, 5

Olga A. Ananina, MD, PhD, Senior Researcher of the Epidemiology Laboratory, 

5, Kooperativny St., 634009, Tomsk

https://orcid.org/0000-0003-2179-5685БоковаУ. А.BokovaU. A.

Бокова Устинья Анатольевна, кандидат биологических наук, научный сотрудник лаборатории биологии опухолевой прогрессии, 

634009, г. Томск, пер. Кооперативный, 5

Ustinia A. Bokova, PhD, Researcher of the Laboratory of Cancer Progression Biology, 

5, Kooperativny St., 634009, Tomsk

https://orcid.org/0000-0003-2923-9755ДенисовЕ. В.DenisovE. V.

Денисов Евгений Владимирович, кандидат биологических наук, заведующий лабораторией биологии опухолевой прогрессии,

634009, г. Томск, пер. Кооперативный, 5

Evgeny V. Denisov, PhD, Head of the Laboratory of Cancer Progression Biology,

5, Kooperativny St., 634009, Tomsk

Научно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наукРоссияCancer Research Institute, Тomsk National Research Medical Center, Russian Academy of SciencesRussian Federation2022291220222163846Copyright © Щеголева А.А., Третьякова М.С., Воробьев Р.С., Ананина О.А., Бокова У.А., Денисов Е.В., 20232023Щеголева А.А., Третьякова М.С., Воробьев Р.С., Ананина О.А., Бокова У.А., Денисов Е.В.Schegoleva A.A., Tretyakova M.S., Vorobyov R.S., Ananina O.A., Bokova U.A., Denisov E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/2371Введение

Введение. Опухоли невыявленной первичной локализации (ОНПЛ) представляют собой метастатические очаги, для которых стандартное диагностическое исследование не позволяет определить первичный опухолевый очаг на момент постановки диагноза. Частота выявления ОНПЛ невысокая, однако данное заболевание характеризуется агрессивностью течения, низкой эффективностью лечения и плохой выживаемостью. Поэтому понимание биологии и механизмов формирования этих злокачественных новообразований является важной задачей.

Цель исследования ‒ идентификация генетических нарушений, характерных для ОНПЛ.

Материал и методы

Материал и методы. В исследовании использовалось полноэкзомное секвенирование образцов ОНПЛ.

Результаты

Результаты. В ОНПЛ обнаружены однонуклеотидные изменения в гене эфринового рецептора EPHA8. Помимо этого, для ОНПЛ были характерны аберрации числа копий ДНК в хромосомных регионах, содержащих гены ID2, FOXD4, ZMYND11, ZNF596, KIDINS220, LRRN1, GEMIN4, CEP72, TPPP и MXRA5. Функциональное аннотирование вышеуказанных генов показало их вовлеченность в транскрипцию, биогенез микроРНК, клеточный цитоскелет, адгезию, ремоделирование внеклеточного матрикса, пролиферацию, апоптоз и эпителиально-мезенхимальный переход.

Заключение

Заключение. Для ОНПЛ характерны нарушения генов, вовлеченных в регуляцию различных биологических процессов, главным образом клеточной миграции. 

Background

Background. Cancer of unknown primary (CUP) is a metastatic lesion with diffcult identifcation of the primary tumor site using standard diagnostic approaches. Although the incidence of CUP is not high, this type of cancer often shows a high aggressiveness and therapy resistance and results in poor patient survival. The mechanisms of CUP origin are not clear, and further studies are needed.

This study aims to analyze the mutational landscape of CUP and identify specifc genetic alterations.

Material and Methods

Material and Methods. Whole exome sequencing was used to analyze the mutational landscape of CUP. Results. CUP had single nucleotide variants (SNVs) in the EPHA8 (ephrin receptor) gene. CUP also harbored copy number variations (CNAs) in the ID2, FOXD4, ZMYND11, ZNF596, KIDINS220, LRRN1, GEMIN4, CEP72, TPPP, and MXRA5 genes. According to functional enrichment analysis, these genes are involved in the regulation of transcription, biogenesis of microRNA, cellular cytoskeleton, adhesion, extracellular matrix remodeling, proliferation, apoptosis, and epithelial-mesenchymal transition.

Conclusion

Conclusion. Cancer of unknown primary harbors mutations in the genes that regulate different biological processes particularly cell motility. 

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