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首页> 外文期刊>European journal of cancer: official journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR) >BRCA1 gene promoter methylation status in high-grade serous ovarian cancer patients - A study of the tumour Bank ovarian cancer (TOC) and ovarian cancer diagnosis consortium (OVCAD)
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BRCA1 gene promoter methylation status in high-grade serous ovarian cancer patients - A study of the tumour Bank ovarian cancer (TOC) and ovarian cancer diagnosis consortium (OVCAD)

机译：高度浆液性卵巢癌患者BRCA1基因启动子甲基化状态-肿瘤库卵巢癌（TOC）和卵巢癌诊断协会（OVCAD）的研究

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Background Mutations in BRCA1/2 genes are involved in the pathogenesis of breast and ovarian cancer. Inactivation of these genes can also be mediated by hypermethylation of CpGs in the promoter regions. Aim of this study was to analyse the clinical impact of BRCA1 promoter gene methylation status in a homogenous cohort of high-grade serous ovarian cancer (HGSOC) patients. Methods The cohort included 257 primary HGSOC patients treated by cytoreduction and platinum-based chemotherapy. DNA was extracted from fresh frozen tissue samples. BRCA1 gene promoter methylation rate was assessed using polymerase chain reaction (PCR). Results 14.8% of patients presented hypermethylation within a selected region of the BRCA1 promoter. The rate of hypermethylation was significantly higher in younger patients (20.8% hypermethylation in the age group ≤58 years versus 8.7% hypermethylation in the age group >58 years; p = 0.008). Optimal tumour debulking could be reached in 63% of patients, without significant differences in the extent of residual disease with respect to the methylation status. No impact of BRCA1 gene promoter methylation status on progression free- and overall-survival rates was found. No significant differences within BRCA1 promoter methylation status between primary and metastatic tissue could be observed. These results on BRCA1 promoter methylation status were also confirmed in a subgroup of 107 patients found negative for BRCA1 exon 11 mutations. Conclusions Our data suggest that BRCA1 methylation determines the earlier onset of HGSOC. Furthermore our study supports the idea that BRCAness is not only due to mutations but also to epigenetic changes in BRCA1 promoter gene.
机译：背景BRCA1 / 2基因的突变与乳腺癌和卵巢癌的发病机理有关。这些基因的失活也可以通过启动子区域中CpG的超甲基化来介导。这项研究的目的是分析BRCA1启动子基因甲基化状态对高级别浆液性卵巢癌（HGSOC）患者的同质队列的临床影响。方法该队列包括257例原发性HGSOC患者，这些患者通过细胞减少术和铂类化学疗法治疗。从新鲜的冷冻组织样品中提取DNA。使用聚合酶链反应（PCR）评估BRCA1基因启动子的甲基化率。结果14.8％的患者在BRCA1启动子的选定区域内出现甲基化过高。年轻患者的高甲基化率明显更高（≤58岁年龄组的高甲基化率为20.8％，而> 58岁年龄组的高甲基化率为8.7％; p = 0.008）。在63％的患者中可以达到最佳的肿瘤减量化，而就甲基化状态而言，残留疾病的程度没有明显差异。没有发现BRCA1基因启动子甲基化状态对无进展生存率和总生存率的影响。在原发和转移组织之间，未观察到BRCA1启动子甲基化状态的显着差异。在BRCA1外显子11突变阴性的107个患者亚组中，也证实了有关BRCA1启动子甲基化状态的这些结果。结论我们的数据表明BRCA1甲基化决定了HGSOC的早期发作。此外，我们的研究支持BRCAness不仅是由于突变，而且还归因于BRCA1启动子基因的表观遗传变化。

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