Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Catalonia Spain.
Epigenetics. 2012 Nov;7(11):1225-9. doi: 10.4161/epi.22561. Epub 2012 Oct 15.
Germline mutations in the BRCA1 or BRCA2 genes are associated with an increased risk of breast and ovarian cancer development. Both genes are involved in DNA repair, and tumors harboring genetic defects in them are thought to be more sensitive to DNA-damaging agents used in chemotherapy. However, as only a minority of breast and ovarian cancer patients carry BRCA1 or BRCA2 mutations, few patients are likely to benefit from these pharmacogenetic biomarkers. Herein, we show that, in cancer cell lines and xenografted tumors, BRCA1 CpG island promoter hypermethylation-associated silencing also predicts enhanced sensitivity to platinum-derived drugs to the same extent as BRCA1 mutations. Most importantly, BRCA1 hypermethylation proves to be a predictor of longer time to relapse and improved overall survival in ovarian cancer patients undergoing chemotherapy with cisplatin.
BRCA1 或 BRCA2 基因中的种系突变与乳腺癌和卵巢癌发展的风险增加有关。这两个基因都参与 DNA 修复，并且携带这些基因遗传缺陷的肿瘤被认为对化疗中使用的 DNA 损伤剂更敏感。然而，由于只有少数乳腺癌和卵巢癌患者携带 BRCA1 或 BRCA2 突变，因此很少有患者可能受益于这些药物遗传学生物标志物。在此，我们表明，在癌细胞系和异种移植肿瘤中，BRCA1 CpG 岛启动子超甲基化相关沉默也预测对铂类药物的敏感性增强，与 BRCA1 突变相同。最重要的是，BRCA1 甲基化证明是接受顺铂化疗的卵巢癌患者复发时间延长和总体生存改善的预测因子。
