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Аннотация
Примерно каждая десятая карцинома молочной железы (РМЖ) развивается в результате наследования патогенной мутации в гене опухолевого супрессора. Более половины РМЖ с признаками наследственной этиологии до сих пор не нашли генетического объяснения. Использование высокопроизводительного секвенирования имеет большой потенциал в плане открытия новых предрасполагающих мутаций. основная проблема полноэкзомных исследований (WES) состоит в дифференциации истинно патогенных каузативных мутаций и нейтральных генных полиморфизмов. Авторами выполнен экзомный анализ 32 образцов ДНК от больных наследственным РМЖ неизвестной генетической этиологии. разработан оригинальный алгоритм селекции кандидатных мутаций с учётом их частоты у онкологических больных и здоровых лиц, потенциальной патогенности мутации, функций гена, молекул-партнёров. В результате был сформирован список из 245 потенциально патогенных наследственных мутаций. В ходе валидирующего молекулярно-эпидемиологического исследования по схеме «случай-контроль» получены данные, которые свидетельствуют о вероятном вкладе в формирование наследственного риска РМЖ нескольких ранее не изучавшихся в этой связи мутаций. Например, мутация BRCA1 p.Gln356Arg в гомозиготном состоянии встречалась у 0.9 % случайных больных РМЖ и была ассоциирована с 7-кратным увеличением риска РМЖ. Это подтверждает существование предрасполагающих к РМЖ генов, действующих по рецессивному механизму.
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