bloodjourГематология и трансфузиологияRussian journal of hematology and transfusiology0234-57302411-3042ООО Издательский дом «Практика»10.18821/0234-5730-2016-61-3-138-143bloodjour-20Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESРезультаты комплексного анализа статуса гена ТР53 у больных диффузной В-крупноклеточной лимфомойThe results of complex analysis of TP53 gene status in patients with diffuse large cell lymphomahttps://orcid.org/0000-0001-7542-7285ВоропаеваЕ. Н.VoropaevaE. N.

Воропаева Елена Николаевна, кандидат мед. наук, старший научный сотрудник лаборатории молекулярно-генетических исследований терапевтических заболеваний 

630089, г. Новосибирск

Voropaeva Elena N., MD, PhD, Senior Researcher of the Laboratory of molecular genetic studies of therapeutic diseases

Novosibirsk, 630089

vena.81@mail.ruhttps://orcid.org/0000-0002-1261-5470ПоспеловаТ. И.PospelovaT. I.

630089, г. Новосибирск

Novosibirsk, 630091

https://orcid.org/0000-0001-9425-413XВоеводаМ. И.VoevodaM. I.

630089, г. Новосибирск

Novosibirsk, 630089

https://orcid.org/0000-0002-7165-4496МаксимовВ. Н.MaksimovV. N.

630089, г. Новосибирск

Novosibirsk, 630089

ФГБНУ НИИ терапии и профилактической медициныРоссияInstitute of Internal and Preventive MedicineRussian FederationГБОУ ВПО Новосибирский государственный медицинский университет Минздрава РоссииРоссияNovosibirsk State Medical UniversityRussian Federation201627022019613138143Copyright © Воропаева Е.Н., Поспелова Т.И., Воевода М.И., Максимов В.Н., 20192019Воропаева Е.Н., Поспелова Т.И., Воевода М.И., Максимов В.Н.Voropaeva E.N., Pospelova T.I., Voevoda M.I., Maksimov V.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.htjournal.ru/jour/article/view/20

В настоящее время отсутствует комплексное описание изменчивости гена ТР53 при диффузной В-крупноклеточной лимфоме (В-ККЛ). В ходе проведенного исследования описаны частота, спектр и функциональная значимость мутаций в гене ТР53 у 74 больных диффузной В-ККЛ г. Новосибирска. Показано, что локализация «горячих точек» мутаций в обследованной выборке больных диффузной В-ККЛ отличалась от данных, представленных в IARC TP53 mutation database. Выявлено наличие при диффузной В-ККЛ патогенетически значимых интронных и сеймсенс-замен. Частота метилирования промотора ТР53 в группе исследования составила 5,8%. Потеря гетерозиготности в гене наблюдалась у 25% больных диффузной В-ККЛ и была отмечена только в подгруппе больных с измененным статусом ТР53 (мутации или метилирование промотора). Полученные результаты свидетельствуют, что при диффузной В-ККЛ происходит селекция функционально значимых мутаций в участках TP53, кодирующих ДНК-связывающий регион, а недостаточность функции данного гена может формироваться по двухударному принципу.

Analysis of the literature shows that there is no comprehensive description of the variability of TP53 gene in diffuse large B-cell lymphoma (DLBCL). The frequency, spectrum and functional significance of mutations in the TP53 gene were investigated at 74 DLBCL patients. The localization of mutations “hot spots” in the studied sample of patients with DLBCL was shown to be differed from the data presented in IARC TP53 mutation database. The occurrence of DLBCL with pathogenetic intron and synonymous replacements was revealed. The frequency of TP53 promoter methylation in the study group was 5.8%. The loss of heterozygosity in the gene was observed in 25% of cases and only in a subset of patients with modified (mutation or promoter methylation) status of the TP53 gene. The results indicate to the selection of functionally significant mutations in the TP53 DNA-binding region in DLBCL. The lack of function of the gene in DLBCL was shown to be possibly formed on the two-hit principle.

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