OncohematologyOncohematologyОнкогематология1818-83462413-4023Publishing House ABV Press47510.17650/1818-8346-2021-16-2-56-69BASIC RESEARCHФУНДАМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯ В ПРАКТИЧЕСКОЙ МЕДИЦИНЕ НА СОВРЕМЕННОМ ЭТАПЕMicrosatellite instability (MSI, EMAST) in the pathogenesis of follicular lymphomaМикросателлитная нестабильность (MSI, EMAST) в патогенезе фолликулярной лимфомыhttps://orcid.org/0000-0001-8053-9724SychevskayaK. A.СычевскаяК. А.
Russian Federation

Kseniya Andreevna Sychevskaia

4 Novyy Zykovskiy Proezd, Moscow 125167

Ксения Андреевна Сычевская

125167 Москва, Новый Зыковский проезд, 4

sychevskaya-ka@yandex.ruhttps://orcid.org/0000-0001-9086-8521KravchenkoS. K.КравченкоС. К.
Russian Federation

4 Novyy Zykovskiy Proezd, Moscow 125167

125167 Москва, Новый Зыковский проезд, 4

https://orcid.org/0000-0003-2957-1619RisinskayaN. V.РисинскаяН. В.
Russian Federation

4 Novyy Zykovskiy Proezd, Moscow 125167

125167 Москва, Новый Зыковский проезд, 4

https://orcid.org/0000-0002-9535-6688MisyurinaА. Е.МисюринаА. Е.
Russian Federation

4 Novyy Zykovskiy Proezd, Moscow 125167

125167 Москва, Новый Зыковский проезд, 4

https://orcid.org/0000-0003-3914-8611NikulinaE. E.НикулинаЕ. Е.
Russian Federation

4 Novyy Zykovskiy Proezd, Moscow 125167

125167 Москва, Новый Зыковский проезд, 4

https://orcid.org/0000-0002-5404-9024BabaevaF. E.БабаеваФ. Э.
Russian Federation

4 Novyy Zykovskiy Proezd, Moscow 125167

125167 Москва, Новый Зыковский проезд, 4

https://orcid.org/0000-0001-9463-9187SudarikovA. B.СудариковА. Б.
Russian Federation

4 Novyy Zykovskiy Proezd, Moscow 125167

125167 Москва, Новый Зыковский проезд, 4

National Medical Research Center for Hematology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России0706202116256690406202104062021https://oncohematology.abvpress.ru/ongm/article/view/475

Background. Genetic instability, an important phenomenon involved in oncogenic transformation and tumor progression, is associated with the insufficiency of the multicomponent DNA repair complex, in particular, the nucleotide mismatch repair (MMR) system. The MMR defect manifests itself as abnormalities in DNA microsatellite repeats, or microsatellite instability (MSI). In the studies of colorectal cancer, the role of MSI in prognostication of the disease, and defining the choice of specific therapy with immune checkpoint inhibitors has been proven.

However, in lymphatic system tumors, the significance of this phenomenon is poorly understood. Determination of genetic instability in the onset of follicular lymphoma, a disease characterized by a heterogeneous course, may have prognostic value.

Objective: to determine the genetic instability at the onset of follicular lymphoma.

Materials and methods. Here we report an analysis of 24 microsatellite repeats and amelogenin loci in tumor cells of 46 follicular lymphoma patients.

Results. In the studied cohort, lesions in microsatellite repeats were presented by MSI in 9 cases (19.6 %) and the loss of heterozygosity (LOH) in 19 cases (41.3 %). Most frequent lesions were found for the SE33 marker located at the q14 locus of chromosome 6. A significant association was shown between MSI and the double-hit follicular lymphoma group with rearrangements of the MYC and BCL2/BCL6 genes.

Conclusion. Thus, our data indicate that the MSI phenomenon might be involved in the pathogenesis of the lymphatic tumors and particularly follicular lymphoma. However further studies on the expanded cohorts of patients are required to define the possible prognostic value of MSI in lymphatic tumors.

Введение. Генетическая нестабильность, играющая важную роль в процессах опухолевой трансформации и прогрессии, ассоциирована с недостаточностью многокомпонентного комплекса репарации ДНК, в частности системы репарации неспаренных нуклеотидов (mismatch repair, MMR). Дефект MMR проявляется в аномалиях микросателлитных повторов ДНК, или микросателлитной нестабильности (microsatellite instability, MSI). На примере колоректального рака была доказана роль MSI в определении прогноза заболевания и выборе специфической терапии ингибиторами иммунных контрольных точек. Однако при опухолях лимфатической системы значение феномена не определено. Для фолликулярной лимфомы – заболевания, протекающего гетерогенно, – исследование генетической нестабильности может быть прогностически значимым.

Цель исследования – определение генетической нестабильности в дебюте фолликулярной лимфомы.

Материалы и методы. В целях определения роли MSI в прогнозе фолликулярной лимфомы проведен анализ 24 микросателлитных повторов и локусов амелогенина у 46 больных.

Результаты. В исследованной когорте аномалии микросателлитных повторов были представлены нестабильностью в 9 (19,6 %) случаях и потерей гетерозиготности – в 19 (41,3 %). С большей частотой встречались нарушения маркера SE33, расположенного в локусе q14 хромосомы 6. Выявлена достоверная ассоциация наличия MSI c перестройками генов MYC и BCL2/BCL6 в группе double-hit фолликулярной лимфомы.

Заключение. Получены результаты, свидетельствующие о существовании феномена MSI при фолликулярной лимфоме и позволяющие предположить его участие в патогенезе данного заболевания.

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