Хромосомная нестабильность при раке желудка

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.

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