Герминальные мутации в генах PALB2 и CHEK2 и наследственный рак

Введение. Не менее 3 % всех случаев рака связаны с наследственными изменениями в генах предрасположенности к злокачественным новообразованиям. Помимо широко известных генов BRCA1,2, в рутинную диагностику внедряются и другие гены, участвующие наравне с BRCA1,2 в системе репарации ДНК и поддержании целостности генома, такие как PALB2, CHEK2. В этом обзоре мы представляем актуальную информацию из последних исследований о строении и функции генов PALB2 и CHEK2, и диагностике мутаций в этих генах, а также об их клиническом значении. Цель работы – актуализация и систематизация данных о генах PALB2 и CHEK2 для лучшего понимания их значения в канцерогенезе, сопряженных с ними рисков развития злокачественных новообразований, профилактики и тактики лечения носителей мутаций.

Материалы и методы. Проведен поиск в базах данных PubMed, Google Scholar, Cyberleninka. Критериями включения статей были новизна и актуальность данных, соответствие тематики обзора. На основании этого было выбрано 79 литературных источников.

Результаты и обсуждение. Мутации в гене PALB2 распространены в 0,5 до 2,1 % случаев рака и ассоциированы с повышенным риском развития рака молочной железы (52,8 % к 80 годам), а также рака яичников (5 %), поджелудочной железы (2,8 %). Частота изменений в гене CHEK2 достигает 5 % и сопряжена с риском развития рака молочной железы (до 40 % к 80 годам) и колоректальным раком. В ходе многочисленных исследований отмечается взаимосвязь наличия мутаций в этих генах и развития рака предстательной железы, легкого, почки и меланомы.

Заключение. Более полное понимание спектра генетической предрасположенности и определение геноспецифических рисков рака может привести к улучшению скрининга, профилактики и терапевтических стратегий для пациентов с наследственным раком и их семей.

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