BRCA1 epigenetic inactivation predicts sensitivity to platinum-based chemotherapy in breast and ovarian cancer.
BRCA1 epigenetic inactivation predicts sensitivity to platinum-based chemotherapy in breast and ovarian cancer.
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BRCA1表观遗传失活预测了乳腺癌和卵巢癌中基于铂的化学疗法的敏感性。
DOI：
10.4161/epi.22561
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发表时间：
2012-11
期刊：
影响因子：
3.7
通讯作者：
Esteller M
中科院分区：
文献类型：
--
作者：
Stefansson OA;Villanueva A;Vidal A;Martí L;Esteller M
BRCA1或BRCA2基因的生殖系突变与乳腺癌和卵巢癌发生风险增加相关。这两种基因都参与DNA修复，并且其中含有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，很少有患者可能从这些药物遗传学生物标志物中获益。在此，我们发现，在癌细胞系和异种移植肿瘤中，BRCA1 CpG岛启动子高甲基化相关沉默也预测了对铂类药物的敏感性增强，其程度与BRCA1突变相同。最重要的是，BRCA1高甲基化被证明是接受顺铂化疗的卵巢癌患者复发时间延长和总生存期改善的预测因子。
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.
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影响因子：
45.3
作者：
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通讯作者：
Kaye, Stan B.
影响因子：
10.3
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Esteller, M;Silva, JM;Herman, JG
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Leenstra, Sieger
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作者：
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