Russian Journal of OncologyRussian Journal of OncologyРоссийский онкологический журнал1028-99842412-9119Eco-Vector11525110.17816/onco115251Clinical investigationsКлинические исследованияResearch ArticleMolecular genetics features of anaplastic thyroid carcinomaМолекулярно-генетические особенности анапластической карциномы щитовидной железыhttps://orcid.org/0000-0003-0986-51508719-8518MusonovaAnastasia K.МусоноваАнастасия Константиновна
Russian Federation
amusonova@mail.ruhttps://orcid.org/0000-0002-9354-87905072-7229NazarovVladimir D.НазаровВладимир Дмитриевич
Russian Federation

MD, Cand. Sci. (Med.)

к.м.н.

nazarov19932@mail.ruhttps://orcid.org/0000-0001-8503-07594978-3190SidorenkoDaria V.СидоренкоДарья Владимировна
Russian Federation
si-do-renko@mail.ruhttps://orcid.org/0000-0002-7570-22561093-3044MusaelyanAram A.МусаелянАрам Ашотович
Russian Federation

Junior Research Associate

младший научный сотрудник

a.musaelyan8@gmail.comhttps://orcid.org/0000-0001-7341-419XAlekseevaEkaterina A.АлексееваЕкатерина Александровна
Russian Federation
kkatealex96@gmail.comhttps://orcid.org/0000-0002-0087-0917KuzovenkovaDaria A.КузовенковаДария Андреевна
Russian Federation
Kuzovenkovadasha@gmail.comhttps://orcid.org/0000-0002-3659-7510KozorezovaEvgeniya S.КозорезоваЕвгения Сергеевна
Russian Federation

MD, Cand. Sci. (Med.)

к.м.н.

pdclient@ncmd.ruhttps://orcid.org/0000-0002-7817-90695920-0603VorobevSergey L.ВоробьевСергей Леонидович
Russian Federation

MD, Cand. Sci. (Med.)

к.м.н.

ncmd@ncmd.ruhttps://orcid.org/0000-0001-6080-80427517-4104OrlovSergey V.ОрловСергей Владимирович
Russian Federation

MD, Dr. Sci. (Med.), Professor, Corresponding Member of the RAS

д.м.н., профессор, член-корреспондент РАН

mail@primatologia.ruhttps://orcid.org/0000-0002-3055-65074458-4633MazingAleksandrа V.МазингАлександра Васильевна
Russian Federation

MD, Cand. Sci. (Med.), Senior Research Associate

к.м.н., старший научный сотрудник

alex_mazing@mail.ruhttps://orcid.org/0000-0002-4998-36999852-7501LapinSergey V.ЛапинСергей Владимирович
Russian Federation

MD, Cand. Sci. (Med.)

к.м.н.

svlapin@mail.ruhttps://orcid.org/0000-0002-2079-04391177-4802EmanuelVladimir L.ЭмануэльВладимир Леонидович
Russian Federation

MD, Dr. Sci. (Med.), Professor

д.м.н., профессор

vladimirem1@gmail.comAcademician I.P. Pavlov First St. Petersburg State Medical UniversityПервый Санкт-Петербургский государственный медицинский университет им. академика И.П. ПавловаResearch Institute of Medical PrimatologyНаучно-исследовательский институт медицинской приматологииNational Center for Clinical Morphological DiagnosticsНациональный центр клинической морфологической диагностики1405202227259700912202216012023Copyright ©; 2023, Musonova A.K., Nazarov V.D., Sidorenko D.V., Musaelyan A.A., Alekseeva E.A., Kuzovenkova D.A., Kozorezova E.S., Vorobev S.L., Orlov S.V., Mazing A.V., Lapin S.V., Emanuel V.L.Copyright ©; 2023, Мусонова А.К., Назаров В.Д., Сидоренко Д.В., Мусаелян А.А., Алексеева Е.А., Кузовенкова Д.А., Козорезова Е.С., Воробьев С.Л., Орлов С.В., Мазинг А.В., Лапин С.В., Эмануэль В.Л.2023Musonova A.K., Nazarov V.D., Sidorenko D.V., Musaelyan A.A., Alekseeva E.A., Kuzovenkova D.A., Kozorezova E.S., Vorobev S.L., Orlov S.V., Mazing A.V., Lapin S.V., Emanuel V.L.Мусонова А.К., Назаров В.Д., Сидоренко Д.В., Мусаелян А.А., Алексеева Е.А., Кузовенкова Д.А., Козорезова Е.С., Воробьев С.Л., Орлов С.В., Мазинг А.В., Лапин С.В., Эмануэль В.Л.https://creativecommons.org/licenses/by-nc-nd/4.0/https://rjonco.com/1028-9984/article/view/115251

INTRODUCTION: Anaplastic thyroid carcinoma (ATC) is the most aggressive type of thyroid cancer accounting for 1–2% of all malignancies. Systemic therapy remains the main treatment strategy. Targeted therapy and immunotherapy are prescribed when certain molecular genetic aberrations are detected.

THE AIM: To investigate the molecular genetic profile of samples of anaplastic thyroid carcinoma.

MATERIALS AND METHODS: The study included 37 patients with ATC. Mutation V600E BRAF, mutations in the gene NRAS and KRAS were detected by allele-specific polymerase chain reaction (AS-PCR). Microsatellite instability (MSI) was determined by fragment analysis in according to ESMO recommendations. Mutations in the promoter region of the TERT gene were used by Sanger sequencing. NTRK1, EML4-ALK, PAX8/PPARy и RET/PTC translocations were determined in all patients with ATC by real-time polymerase chain reaction (PCR).

RESULTS: According to the results of the study, the frequency of the V600E mutation in the BRAF gene was 32.4% (12/37). The frequency of aberrations in the NRAS, KRAS genes in anaplastic thyroid carcinoma was 13.5% (n=5). The prevalence of point mutations in the promoter gene TERT in food samples of ATC was 24.3% (n=9). MSI was found in 2.7% (1/37) of cases of anapalastic thyroid carcinoma. NTRK1, EML4-ALK, PAX8/PPARy and RET/PTC translocations were not detected in cases with anaplastic thyroid carcinoma.

CONCLUSION: The further study of the main specific molecular targets in cancer cells will allow to personalize the tactics of patients with anaplastic thyroid carcinoma.

Обоснование. Анапластическая карцинома щитовидной железы (АКЩЖ) представляет собой наиболее агрессивный тип рака щитовидной железы, на долю которого приходится 1–2% случаев всех злокачественных опухолей. Основной стратегией лечения остаётся системная терапия, в частности новые подходы, такие как таргетная терапия и иммунотерапия, которые назначаются при выявлении определённых молекулярно-генетических аберраций.

Цель. Изучить молекулярно-генетический профиль образцов анапластической карциномы щитовидной железы.

Материалы и методы. Исследование включало 37 пациентов с установленным диагнозом АКЩЖ. Выявляли мутации в гене ВRAF (V600E), а также в генах NRAS и KRAS с помощью аллель-специфической полимеразной цепной реакции (ПЦР). В исследуемых образцах определяли наличие микросателлитной нестабильности (MSI) с помощью фрагментного анализа в соответствии с рекомендациями ESMO. Мутации в промотерном регионе гена TERT выявляли с использованием секвенирования по Сэнгеру. Всем пациентам определяли транслокации гена NTRK1, EML4-ALK, PAX8/PPARy и RET/PTC с помощью метода ПЦР в режиме реального времени.

Результаты. По результатам исследования частота встречаемости мутации V600E в гене ВRAF составила 32,4% (12/37). Общая распространённость аберраций в генах семейства RAS при АКЩЖ составила 13,5% (n=5). Распространённость точечных мутаций в промотерном регионе гена TERT в исследуемых образцах АКЩЖ составила 24,3% (n=9). MSI обнаружена в 2,7% случаев (1/37) АКЩЖ. Транслокаций гена NTRK1, EML4-ALK, PAX8/PPARy и RET/PTC в исследуемых образцах анапластической карциномы щитовидной железы не найдено.

Заключение. Дальнейшее исследование основных молекулярно-генетических мишеней позволит персонализировать тактику ведения пациентов с АКЩЖ.

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