Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press46010.17650/2313-805X-2022-9-3-69-84RESEARCH ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИMutation profile of diffuse large B-cell lymphoma with relapses in the central nervous systemМутационный профиль диффузной В-крупноклеточной лимфомы с рецидивами в центральной нервной системеhttps://orcid.org/0000-0001-7542-7285VoropaevaE. N.ВоропаеваЕ. Н.
Russian Federation

Elena N. Voropaeva.

175/1 Boris Bogatkov St., Novosibirsk 630089; 52 Krasny Prospekt, Novosibirsk 630091.

Воропаева Елена Николаевна.

630089 Новосибирск, ул. Бориса Богаткова, 175 / 1; 630091 Новосибирск, Красный проспект, 52.

vena.81@mail.ruPospelovaT. I.ПоспеловаТ. И.
Russian Federation

52 Krasny Prospekt, Novosibirsk 630091.

630091 Новосибирск, Красный проспект, 52.

https://orcid.org/0000-0001-6887-3172KarpovaV. S.КарповаВ. С.
Russian Federation

52 Krasny Prospekt, Novosibirsk 630091.

630091 Новосибирск, Красный проспект, 52.

https://orcid.org/0000-0002-1301-5944ChurkinaM. I.ЧуркинаМ. И.
Russian Federation

52 Krasny Prospekt, Novosibirsk 630091.

630091 Новосибирск, Красный проспект, 52.

VyatkinYu. V.ВяткинЮ. В.
Russian Federation

1 Pirogova St., Novosibirsk 630090.

630090 Новосибирск, ул. Пирогова, 1.

https://orcid.org/0000-0001-7933-8394AgeevaT. A.АгееваТ. А.
Russian Federation

52 Krasny Prospekt, Novosibirsk 630091.

630091 Новосибирск, Красный проспект, 52.

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

175/1 Boris Bogatkov St., Novosibirsk 630089. 

630089 Новосибирск, ул. Бориса Богаткова, 175 / 1.

Scientific Research Institute of Therapy and Preventive Medicine — branch of the Federal Research Center Institute of Cytology and Genetics of the Siberian branch of the Russian Academy of SciencesНаучно-исследовательский институт терапии и профилактической медицины – филиал ФГБНУ «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»Novosibirsk State Medical University, Ministry of Health of RussiaФГБОУ ВО «Новосибирский государственный медицинский университет» Минздрава РоссииNovosibirsk National Research State UniversityФГАОУ ВО «Новосибирский национальный исследовательский государственный университет»150920229369840710202207102022Copyright ©; 2022, Voropaeva E.N., Pospelova T.I., Karpova V.S., Churkina M.I., Vyatkin Y.V., Ageeva T.A., Maksimov V.N.Copyright ©; 2022, Воропаева Е.Н., Поспелова Т.И., Карпова В.С., Чуркина М.И., Вяткин Ю.В., Агеева Т.А., Максимов В.Н.2022Voropaeva E.N., Pospelova T.I., Karpova V.S., Churkina M.I., Vyatkin Y.V., Ageeva T.A., Maksimov V.N.Воропаева Е.Н., Поспелова Т.И., Карпова В.С., Чуркина М.И., Вяткин Ю.В., Агеева Т.А., Максимов В.Н.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/460

Introduction. The recurrence of diffuse large B-cell cell lymphoma in the central nervous system in the vast majority of cases is a fatal manifestation of the disease. The study of the lymphoma mutational profile can improve the accuracy of the prognosis of relapse in the central nervous system and justify the selection of patients for preventive treatment. Aim. To evaluate the mutational profile of cases of diffuse large B-cell cell lymphoma with central nervous system damage in relapse based on the results of our own experiment on high-performance sequencing.

Materials and methods. On the Illumina platform, full-exome sequencing of diagnostic samples of diffuse large B-cell cell lymphoma with relapses in the central nervous system was performed. A panel including more than 70 genes was analyzed.

Results. Four main groups of genetic events can be distinguished in the group of studied samples, namely: combined mutations in the NF-kB (MYD88, NOTCH1, CD79B, CARD11) and JAK-STAT (PIM1, STAT6) signaling pathways, as well as aberrations in the main oncosuppressor TP53 and chromatin remodeling system genes (ARID1A, KMT2D, EP300, SMARCA4). A recurrent mutation c. 794T>C, p.L265P MYD88 was detected in the study group. Among other findings, mutations in the CIITA and CD58 genes should be noted, which are important in avoiding tumor cells from immune surveillance.

Conclusion. Despite the apparent heterogeneity of the mutational profile of diffuse large B-cell cell lymphoma with relapses in the central nervous system, in most cases, tumor cells were characterized by genetic disorders leading to the production of a large number of pro-inflammatory cytokines by malignant lymphocytes, as well as aberrations that reduce immunogenicity and contribute to the avoidance of immune surveillance by the tumor.

Введение. Рецидив диффузной в-клеточной крупноклеточной лимфомы в центральной нервной системе в подавляющем большинстве случаев является фатальным проявлением заболевания. изучение мутационного профиля лимфомы может способствовать улучшению точности прогноза рецидива в центральной нервной системе и обоснованию отбора пациентов для профилактического лечения.

Цель исследования - изучить мутационный профиль случаев диффузной в-клеточной крупноклеточной лимфомы с рецидивами в центральной нервной системе.

Материалы и методы. На платформе Illumina выполнено полноэкзомное секвенирование диагностических образцов диффузной в-клеточной крупноклеточной лимфомы с рецидивами в центральной нервной системе. проанализирована панель, включающая более 70 генов.

Результаты. можно выделить 4 основные группы генетических событий в исследованных образцах, а именно: сочетанные мутации в генах сигнальных путей NF-кВ (MYD88, NOTCH1, CD79B, CARD11) и JAK-STAT (PIM1, STAT6), а также аберрации в главном онкосупрессоре ТР53 и генах системы ремоделирования хроматина (ARID1A, KMT2D, EP300, SMARCA4). в группе исследования выявлена рекуррентная мутация c. 794T>C, p.L265P MYD88. Среди других находок следует отметить мутации в генах CIITA и CD58, имеющих значение в уклонении опухолевых клеток от иммунного надзора.

Заключение. Несмотря на кажущуюся гетерогенность мутационного профиля диффузной в-клеточной крупноклеточной лимфомы с рецидивами в центральной нервной системе, в большинстве случаев для опухолевых клеток были характерны генетические нарушения, приводящие к продукции злокачественными лимфоцитами большого количества провоспалительных цитокинов, а также аберрации, снижающие иммуногенность и способствующие избеганию опухолью иммунного надзора.

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