Head and Neck TumorsHead and Neck TumorsОпухоли головы и шеи2222-14682411-4634Publishing House ABV Press61210.17650/2222-1468-2021-11-1-78-85ORIGINAL REPORTОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕMutation profile of the tall cell variant of papillary thyroid carcinoma: analysis of 5 cases using wide-panel next-generation sequencingМутационный профиль папиллярного рака щитовидной железы из высоких клеток: результаты анализа 5 случаев с использованием широкопанельного таргетного секвенированияhttps://orcid.org/0000-0001-6600-0933PlaksaI. L.ПлаксаИ. Л.
Russian Federation

37 Liteyny Ave., St. Petersburg 191014; Bld. 1, 3 Gubkina St., Moscow 119333

191014 Санкт-Петербург, Литейный проспект, 37; 119333 Москва, ул. Губкина, 3, корп. 1

https://orcid.org/0000-0001-6684-2532SavchukM. R.СавчукМ. Р.
Russian Federation

Maria Ruslanovna Savchuk

Bld. 1, 3 Gubkina St., Moscow 119333; 9 Vysokovoltnaya St., Ryazan 390026

Мария Руслановна Савчук

119333 Москва, ул. Губкина, 3, корп. 1; 390026 Рязань, ул. Высоковольтная, 9

savchuk@genetico.ruhttps://orcid.org/0000-0001-6462-1875ShvedN. V.ШведН. В.
Russian Federation

41 Kirochnaya St., St. Petersburg 191015

191015Санкт-Петербург, ул. Кирочная, 41

SavelovN. A.СавеловН. А.
Russian Federation

27, Istra 143423, Stepanovskoye Stlmt, Krasnogorsky Dstr., Moscow Region

Московская область, Красногорский р-н, п/о Степановское, 143423 Истра, 27

https://orcid.org/0000-0002-4673-1031KhmelkovaD. N.ХмельковаД. Н.
Russian Federation

Bld. 1, 3 Gubkina St., Moscow 119333

119333 Москва, ул. Губкина, 3, корп. 1

https://orcid.org/0000-0001-5848-5117IsaevА. A.ИсаевА. А.
Russian Federation

Bld. 1, 3 Gubkina St., Moscow 119333

119333 Москва, ул. Губкина, 3, корп. 1

https://orcid.org/0000-0001-8389-3841DeevR. V.ДеевР. В.
Russian Federation

41 Kirochnaya St., St. Petersburg 191015

191015Санкт-Петербург, ул. Кирочная, 41

Leningrad Regional Clinical Oncological DispensaryГБУЗ Ленинградский областной клинический онкологический диспансерCenter of Genetics and Reproductive Medicine GeneticoЦентр генетики и репродуктивной медицины Генетико, ОООI.P. Pavlov Ryazan State Medical University, Ministry of Health of RussiaФГБОУ ВО Рязанский государственный медицинский университет им. акад. И.П. Павлова Минздрава РоссииNorth-Western State Medical University n. a. I.I. Mechnikov, Ministry of Health of RussiaФГБОУ ВО Северо-Западный государственный медицинский университет им. И.И. Мечникова Минздрава РоссииMoscow City Oncological Hospital No. 62, Moscow Healthcare DepartmentГБУЗ Московская городская онкологическая больница № 62 Департамента здравоохранения г. Москвы2404202111178852304202123042021Copyright ©; 2021, Plaksa I.L., Savchuk M.R., Shved N.V., Savelov N.A., Khmelkova D.N., Isaev А.A., Deev R.V.Copyright ©; 2021, Плакса И.Л., Савчук М.Р., Швед Н.В., Савелов Н.А., Хмелькова Д.Н., Исаев А.А., Деев Р.В.2021Plaksa I.L., Savchuk M.R., Shved N.V., Savelov N.A., Khmelkova D.N., Isaev А.A., Deev R.V.Плакса И.Л., Савчук М.Р., Швед Н.В., Савелов Н.А., Хмелькова Д.Н., Исаев А.А., Деев Р.В.https://creativecommons.org/licenses/by/4.0https://ogsh.abvpress.ru/jour/article/view/612

The study objective is to analyze the mutation profile of the tall cell variant (TCV) of papillary thyroid carcinoma (PTC).

Materials and methods. The main inclusion criteria according to the WHO classification (2017) was PTC composed of at least 30 % of tall cells. Genetic examination was conducted using the FoundationOne CDx assay (USA) with median depth of coverage of >500x. This study included 5 patients (1 man and 4 women) with a mean age of 52.6 years (range: 48-56 years). The tumor size varied between 0.4 x 0.5 cm and 11.0 x 9.0 cm. All patients have undergone surgical treatment: hemithyroidectomy for patient No. 1 with a small tumor (pT1b); thyroidectomy for patient No. 2 (pT3b); extensive thyroidectomy with the removal of paratracheal tissue for patients No. 3, 4, and 5 (No. 3 - pT3bN0; No. 4 - pT3bN1b; No. 5 - pT3bN1b). Three out of the five patients also had adenomatous goiter. The mean follow-up time was 3.4 to 5.2 years.

Results. Tumors in all patients were characterized by low mutational load (0 to 4 mutations per 1 million nucleotides (megabase)) and no microsatellite instability. All study participants were found to have p.V600E mutation in the BRAF gene; two patients had c.-124C>T mutation in the promoter region of the TERT gene. All patients carried mutations with unknown clinical significance: p.V562I in the EPHB1 gene (in 2 patients); mutations in the genes AR, CREBBP, EP300, ERCC4, FLT1, IKBKE, JAK2, MAF, MLL2, MST1R, MYC, MYCL1, NTRK2, TSC2 (each mutation registered in one patient). One individual with the largest tumor and the most aggressive disease was found to have amplifications of the BTG2, MAP3K1, SMAD2, and TBX3 genes.

Conclusion. In 5 patients analyzed in this study, the mutation profile of TCV PTC was characterized by low mutational load, no microsatellite instability, and presence of p.V600E mutation in the BRAF gene in all cases. Some patients also had c.-124C>T mutation in the TERT gene and p.V562I mutation in the EPHB1 gene.

Цель исследования - оценить мутационный профиль случаев папиллярного рака щитовидной железы из высоких клеток.

Материалы и методы. Основным критерием включения в группу анализа было наличие высококлеточного компонента в количестве не менее 30 % от общего объема опухоли. Генетическое исследование выполнялось с использованием диагностического теста FoundationOne CDx (США) со средней глубиной покрытия >500x. В исследование было включено 5 пациентов (1 мужчина и 4 женщины, средний возраст 52,6 года (48-56 лет)). Размеры опухоли варьировали от 0,4 х 0,5 до 11,0 х 9,0 см. Все пациенты получали оперативное лечение, у пациента № 1 ввиду небольшого размера узла была выполнена гемитиреоидэктомия (pT1b), у пациента 2 -тиреоидэктомия (pT3b), у пациентов № 3, 4 и 5 - расширенная тиреоидэктомия с удалением паратрахеальной клетчатки (№ 3 - pT3bN0; № 4 - pT3bN1b; № 5 - pT3bN1b). У 3 из 5 пациентов фоновым заболеванием был аденоматозный зоб. Наблюдение за пациентами продолжалось от 3,4 до 5,2 года.

Результаты. Опухоли всех пациентов характеризовались низкой мутационной нагрузкой - от 0 до 4 мутаций на 1 млн нуклеотидов (мегабазу) и отсутствием микросателлитной нестабильности. У всех пациентов была выявлена мутация p.V600E в гене BRAF, у 2 пациентов была обнаружена мутация в промоторе гена TERT c.-124C>T. У всех пациентов были выявлены мутации с неизвестным клиническим значением: p.V562I в гене EPHB1 (у 2 пациентов); мутации в генах AR, CREBBP, EP300, ERCC4, FLT1, IKBKE, JAK2, MAF, MLL2, MST1R, MYC, MYCL1, NTRK2, TSC2 (каждая из мутаций - у 1 пациента). У одного из пациентов с наибольшим размером опухоли и наиболее агрессивным течением были обнаружены амплификации генов BTG2, MAP3K1, SMAD2, TBX3.

Заключение. В 5 изученных случаях мутационный профиль папиллярного рака из высоких клеток характеризуется низкой мутационной нагрузкой, отсутствием микросателлитной нестабильности и наличием во всех случаях мутации p.V600E гена BRAF, которая у части пациентов сочеталась с мутацией c.-124C>T в гене TERT и p.V562I в гене EPHB1.

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