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Mức độ đột biến soma tăng cao ở một người mang đột biến BRCA1 biểu hiện
Tóm tắt
Sự mất hoạt động đồng hợp tử của các gen gây ung thư vú BRCA1 và BRCA2 (FANCD1) làm tăng khả năng nhạy cảm với các đột phá đôi chuỗi DNA, nhưng kiểu gen này chỉ xảy ra trong khối u, sau khi mất dị hợp tử ở một trong những locus này. Do đó, nếu những gen này đóng vai trò trong nguyên nhân gây ung thư thì chúng phải thể hiện một kiểu hình dị hợp tử ở cấp độ tế bào. Để điều tra các hậu quả tiềm năng của sự dị hợp sắc thể soma đối với một đột biến BRCA1 liên quan đến sinh carcinôm vú trên gánh nặng đột biến soma cơ bản, chúng tôi đã áp dụng hai xét nghiệm tiêu chuẩn về đột biến soma ở người sống để phân tích mẫu máu từ một người mang đột biến Q1200X ở BRCA1, khối u của người này được xác định độc quyền thông qua một nghiên cứu sàng lọc MRI. Bệnh nhân có tần suất đột biến mất alen là 19.4 × 10−6 ở locus GPA lặn tự, và 17.1 × 10−6 ở locus HPRT liên kết với X trong bạch cầu. Cả hai tần suất đột biến này đều cao hơn mong đợi so với các đối chứng không bệnh cùng độ tuổi (P<0.05). Tần suất đột biến ở locus HPRT cũng cao tương tự trong các dòng tế bào lymphoblastoid được thiết lập từ ba người mang đột biến BRCA1 khác có ung thư vú. Tần suất đột biến GPA của bệnh nhân dưới mức được thiết lập để chẩn đoán bệnh nhân bệnh Fanconi đồng hợp tử, nhưng nhất quán với dữ liệu từ những người dị hợp bắt buộc. Tần suất đột biến HPRT tăng cao hơn có phần gợi nhớ đến dữ liệu từ các bệnh nhân mắc bệnh xeroderma pigmentosum, một bệnh được đặc trưng bởi độ nhạy cảm với UV và thiếu hụt trong con đường sửa chữa DNA bằng cách cắt bỏ nucleotide. Do đó, bệnh nhân mắc ung thư vú liên quan đến BRCA1 này thể hiện một kiểu hình độc nhất của việc tăng cường đột biến nền có thể đã góp phần vào sự phát triển của bệnh độc lập với sự mất dị hợp tử ở locus nhạy cảm.
Từ khóa
#ung thư vú #đột biến BRCA1 #dị hợp tử #đột biến soma #gánh nặng đột biếnTài liệu tham khảo
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