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Внедрение технологии секвенирования нового поколения позволило охарактеризовать молекулярный портрет рака предстательной железы (РПЖ) и обнаружить высокую частоту нарушений в генах репарации ДНК, в том числе участниках гомологичной рекомбинации (Homologous Recombination Repair, HRR), при опухолях этой локализации. Анализ статуса генов HRR приобрел особую актуальность после внедрения в практику терапии метастатического кастрационно-резистентного РПЖ ингибиторов поли(АДФ-рибоза)-полимеразы (PARP-ингибиторов). Эти препараты одобрены к применению при наличии мутаций в генах BRCA1/2 и ряде других компонентов системы репарации ДНК. В то время как предиктивное значение повреждений BRCA1 и BRCA2 не вызывает сомнений, клиническая польза PARP-ингибиторов в присутствии других нарушений HRR является более спорной. Помимо персонализации терапии, генетический анализ HRR позволяет выявить наследственные формы РПЖ. Настоящий обзор посвящен характеристике и клинической значимости мутаций в различных генах HRR.
Библиографические ссылки
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