Russian Journal of BiotherapyRussian Journal of BiotherapyРоссийский биотерапевтический журнал1726-97841726-9792Publishing House ABV Press114110.17650/1726-9784-2019-18-1-50-59ORIGINAL REPORTSОРИГИНАЛЬНЫЕ СТАТЬИComplex cytogenetic research of cryptic chromosomal aberrations in patients with multiple myelomaКомплексное цитогенетическое исследование хромосомных аберраций у больных множественной миеломойhttps://orcid.org/0000-0001-8399-057XSolodovnikA. A.СолодовникА. А.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское ш., 24

https://orcid.org/0000-0002-0638-213XMkrtchyanА. S.МкртчянА. С.
Russian Federation

104 Profsojuznaya St., Moscow 117279

117279 Москва, Профсоюзная ул., 104

https://orcid.org/0000-0002-0762-5631MisyurinV. A.МисюринВ. А.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское ш., 24

https://orcid.org/0000-0001-8277-8649KesaevaL. A.КесаеваЛ. А.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское ш., 24

https://orcid.org/0000-0002-4735-977XKasatkinaN. N.КасаткинаН. Н.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское ш., 24

VotyakovaO. M.ВотяковаО. М.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское ш., 24

YakimovichO. Yu.ЯкимовичО. Ю.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское ш., 24

https://orcid.org/0000-0001-9615-6090MedvedovskayaE. G.МедведовскаяЕ. Г.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское ш., 24

https://orcid.org/0000-0002-1731-8336AntipovaA. S.АнтиповаА. С.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское ш., 24

https://orcid.org/0000-0001-6674-8634ZavodnovaI. Z.ЗаводноваИ. З.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское ш., 24

https://orcid.org/0000-0003-3430-8540KolomeytsevO. A.КоломейцевО. А.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское ш., 24

https://orcid.org/0000-0003-3244-7774ShirinA. D.ШиринА. Д.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478

115478 Москва, Каширское ш., 24

https://orcid.org/0000-0002-3067-1601OsmanovE. A.ОсмановЕ. А.
Russian Federation

Build. 2, 8 Trubetskaya St., Moscow 119991

119991 Москва, ул. Трубецкая, 8, стр. 2

https://orcid.org/0000-0003-1349-2879MisyurinA. V.МисюринА. В.
Russian Federation

24 Kashirskoe Shosse, Moscow 115478;104 Profsojuznaya St., Moscow 117279

115478 Москва, Каширское ш., 24;117279 Москва, Профсоюзная ул., 104

N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian FederationФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава РоссииLLC GeneTechnologyООО «ГеноТехнология»Sechenov First Moscow State Medical University of the Ministry of Health of the Russian FederationФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет)N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian FederationФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России ООО «ГеноТехнология»LLC GeneTechnology1904201918150591904201919042019https://bioterapevt.abvpress.ru/jour/article/view/1141

Background . Multiple myeloma (MM) is a malignant lymphoproliferative B-cell disease characterization by clonal proliferation of plasma cells in the bone marrow and beyond its borders. Currently, a wide range of cytogenetic anomalies and molecular-biological parameters are studied as prognostic factors.Objective: a comparative study of the frequency, features and clinical significance of chromosomal abnormalities in MM by conventional cytogenetic and fluorescent in situ hybridization (FISH) methods.Materials and methods . 77 patients with MM, which admitted in N.N. Blokhin National Medical Research Center of Oncology, were included in the study from 2016 to 2017.Results . Chromosomal alterations were detected only in one case (1/77) by conventional cytogenetic method G-banding. However cytogenetic aberrations were revealed in 26 % of cases (20/77) using FISH. Deletions of different regions of chromosomes, indicating the possible presence of a hypodiploid clone or loss of some regions, were found in one patient in the second FISH analysis after 6 months. In the cohort of patients with chromosomal abnormalities (n = 20) a partial trisomy 11q, a deletion of the region q32 of the chromosome 14, a translocation t(4;14)(p16;q32) and IGHV gene rearrangement were determined in 30 % (6/20) as sole anomalies. Two or more cytogenetic aberrations were identified in the remaining 14 patients. Our study confirms that chromosomal abnormalities are more likely detected at later stages of MM (IA и IIA – 0 %, IIIA и IIIВ – 27 and 47 % respectively).Conclusion . FISH allows to detect chromosomal changes in tumor plasma cells regardless of the mitosis phase. In MM, it becomes particularly important in connection with low proliferative activity of plasma cells. Additionally, in the fourth of MM patients in the study submicroscopic chromosomal aberrations were discovered using FISH. The improvement of the probe panel and the widespread use of locus specific FISH don’t replace G-banding that allows to see damages of all chromosomes at once.

Актуальность . Множественная миелома (ММ) – злокачественное В-клеточное лимфопролиферативное заболевание с клональной пролиферацией плазматических клеток, продуцирующих моноклональный иммуноглобулин, в костном мозге и за его пределами. В настоящее время в качестве прогностических факторов исследуется широкий спектр цитогенетических аномалий и молекулярно-биологических параметров.Цель работы – сравнительное исследование частоты, характера и клинической значимости хромосомных нарушений при ММ методами стандартной цитогенетики и флуоресцентной in situ гибридизации (FISH).Материалы и методы . В исследование включены 77 больных с ММ, наблюдавшихся в ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России в 2016–2017 гг. Пациенты были в возрасте от 34 до 77 лет, медиана – 53 года. Женщин было 42 (54,5 %), мужчин – 35 (45,5 %).Результаты . Метод стандартного кариотипирования (G-бэндинг) позволил выявить хромосомные изменения лишь у 1 из 77 больных. Однако методом FISH были обнаружены хромосомные аберрации уже у 26 % пациентов (20 из 77). Делеции различных участков исследуемых локусов хромосом, свидетельствующих о возможном наличии гиподиплоидного клона или потери отдельных регионов, обнаружены у 1 больного только при повторном обследовании с интервалом 6 мес. Среди пациентов с хромосомными нарушениями (n = 20) аномалии типа частичной трисомии 11q, делеции участка q32 хромосомы 14, транслокации t(4;14)(р16;q32) и перестройки генов IGHV обнаружены у 30 % (6 из 20). У 14 из 20 больных выявлены 2 и более хромосомных нарушения. Хромосомные аномалии с большей частотой обнаруживаются на более поздних стадиях ММ (IA и IIA стадии – 0 % наблюдений с аберрациями, IIIA и IIIВ – 27 и 47 % соответственно).Заключение . FISH позволяет обнаружить хромосомные нарушения в опухолевых плазматических клетках независимо от фазы митоза. При ММ это приобретает особо важное значение в связи с низкой пролиферативной активностью плазмоцитов. Кроме того, FISH позволяет обнаружить субмикроскопические, т. е. скрытые хромосомные аберрации, которые встречаются у трети больных ММ. Совершенствование панели зондов и широкое применение FISH не означает пренебрежение методами стандартной цитогенетики. G-бэндинг позволяет увидеть нарушения сразу всех хромосом в отличие от локус-специфичного FISH-анализа.

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