medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2024.05.3-14medgen-2473Research ArticleНАУЧНЫЙ ОБЗОРREVIEWХромосомная нестабильность при раке желудкаChromosomal instability in gastric cancerНемцоваМ. В.NemtsovaM. V.

19048, г. Москва, ул. Трубецкая, д. 8, стр. 2 ; 115522, г. Москва, ул. Москворечье, д. 1

8-2, Trubetskaya st., Moscow, 119991; 1, Moskvorechye st., Moscow, 115522

nemtsova_m_v@mail.ruМолчановА. Д.MolchanovA. D.

19048, г. Москва, ул. Трубецкая, д. 8, стр. 2 ; 115478, г. Москва, Каширское шоссе, д. 23

8-2, Trubetskaya st., Moscow, 119991; 23, Kashirskoe shosse, Moscow, 115478

КузнецоваЕ. Б.KuznetsovaE. B.

19048, г. Москва, ул. Трубецкая, д. 8, стр. 2 ; 115522, г. Москва, ул. Москворечье, д. 1

8-2, Trubetskaya st., Moscow, 119991; 1, Moskvorechye st., Moscow, 115522

БуреИ. В.BureI. V.

119048, г. Москва, ул. Трубецкая, д. 8, стр. 2; 125993, г. Москва, ул. Баррикадная, д.2/1, стр.1 

8-2, Trubetskaya st., Moscow, 119991; 2/1 Barrikadnaya st., Moscow, 125993

Первый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский университет); ФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова»РоссияI.M. Sechenov First Moscow state medical university; N.P. Bochkov Research Centre for Medical GeneticsRussian FederationПервый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский университет); ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Министерства здравоохранения Российской ФедерацииРоссияI.M. Sechenov First Moscow state medical university; N.N. Blokhin National Medical Research Center of OncologyRussian FederationПервый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский университет); ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской ФедерацииРоссияI.M. Sechenov First Moscow state medical university; Russian Medical Academy of Continuous Professional EducationRussian Federation202402082024235314Copyright © Немцова М.В., Молчанов А.Д., Кузнецова Е.Б., Буре И.В., 20242024Немцова М.В., Молчанов А.Д., Кузнецова Е.Б., Буре И.В.Nemtsova M.V., Molchanov A.D., Kuznetsova E.B., Bure I.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/2473

В исследовании The Cancer Genome Atlas (TCGA) с учетом выявляемых методом полноэкзомного секвенирования изменений копийности хромосомных локусов, экспрессии генов, метилирования ДНК и активности белков предложена молекулярная классификация рака желудка на четыре подтипа: подтип, ассоциированный с вирусом Эпштейна-Барр (EBV+), подтип, ассоциированный с микросателлитной нестабильностью (MSI), хромосомно-нестабильный подтип (CIN) и геномно стабильный подтип (GS). Однако в настоящее время подтип CIN недостаточно охарактеризован и не имеет эффективных и удобных маркеров для диагностики, молекулярной и гистологической верификации. Подтип CIN характеризуется наличием хромосомной нестабильности, которая проявляется повышенной частотой анеуплоидий и/или структурных хромосомных перестроек в опухолевых клетках. Структурные перестройки при раке желудка CIN являются неслучайными и выявляются в определенных хромосомных локусах, которые часто подвергаются перестройкам в результате определенной структурной организации. В обзоре рассмотрены молекулярные механизмы и возможные причины, приводящие к появлению хромосомной нестабильности в опухолях желудка, представлены характерные перестройки хромосомных локусов и их влияние на развитие и клиническое течение заболевания, а также перечислены драйверные гены, их функции и возможности их таргетирования.

The Cancer Genome Atlas (TCGA), using approaches based on the analysis of full-exome sequencing, changes in the copy of chromosomal loci, gene expression, DNA methylation and protein activity, proposed a molecular classification of gastric cancer into four subtypes: the subtype associated with Epstein-Barr virus (EBV+), the subtype associated with microsatellite instability (MSI), chromosomally unstable subtype (CIN) and genomically stable subtype (GS). However, the subtype of GC with chromosomal instability is still insufficiently described and does not have effective and convenient markers for diagnosis, molecular and histological verification. The CIN subtype of GC is characterized by the presence of chromosomal instability, which is manifested by an increased frequency of aneuploidies and/or structural chromosomal rearrangements in tumor cells. Structural rearrangements in CIN subtype of GC are not accidental and are detected in certain chromosomal loci, which are often subject to rearrangements as a result of a certain structural organization. The review considers the molecular mechanisms and possible causes leading to the appearance of chromosomal instability in GC, presents the common rearrangements of chromosomal loci and their impact on the development and clinical course of the disease, as well as lists the driver genes, their functions and the possibilities of targeting them in CIN subtype of GC. 

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