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摘要
Ассоциация генетических драйверных изменений в гастроинтестинальных стромальных опухолях (ГИСО) с клиническими последствиями является наиболее изученным аспектом в биологии солидных опухолей. Генотипирование отдельных экзонов cKIT и PDGFRA вошло в стандартную практику диагностики и лечения ГИСО. В обзоре проведен анализ современных представлений о молекулярно-генетических механизмах и маркерах, лежащих в основе профилирования ГИСО. Особый интерес представляют опухоли дикого типа по c-KIT и PDGFRA, в которых обнаруживают активирующие мутации онкогенов RAS, BRAF и EGFR, ассоциированные с ранними стадиями прогрессирования заболевания. Приведены данные исследований генетических и эпигенетических изменений при ГИСО, выявивших прогностическое значение инактивации CDKN2A и р53, делеций 22q, 1p и 15q, CpG-гиперметилирования. Описаны новые факторы, определяющие высокий риск прогрессирования ГИСО: инактивация дистрофина, гипометилирование ДНК, изменение экспрессии микрорнк и HOTAIR. Достигнутый прогресс в понимании молекулярных механизмов гисо открывает возможность разработки и эффективного применения новых терапевтических подходов, расширения спектра молекулярно-генетических маркеров, определяющих тактику ведения больных.
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