Detection of aberrant methylation of four genes in plasma DNA for the detection of breast cancer
Detection of aberrant methylation of four genes in plasma DNA for the detection of breast cancer
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DOI：
10.1200/jco.2005.01.3516
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发表时间：
2006-09-10
影响因子：
45.3
通讯作者：
Sidransky, David
中科院分区：
文献类型：
--
作者：
Hoque, Mohammad O.;Feng, Qinghua;Sidransky, David
乳腺癌筛查的新方法是必要的，特别是在发展中国家，乳房x光检查是不可行的。在这项研究中，我们探索了基于血液的生物标志物可能成为乳腺癌生物标志物的假设。患者和方法我们首先确定了四个候选基因（APC、GSTP1、Rassf1A和RAR β 2）在西非主要晚期乳腺癌妇女原发性乳腺癌组织中的异常甲基化频率。我们使用高通量DNA甲基化试验（定量甲基化特异性聚合酶链反应）检测了93名乳腺癌妇女和76名对照者的血浆中是否存在四种甲基化基因。样本被随机均匀地分为训练数据集和验证数据集。基于血浆的检测和基因面板的基因阳性截止值由训练数据集中的受试者工作特征曲线确定，随后在验证数据集中作为筛选工具进行评估。结果至少一个基因的甲基化导致敏感性62%，特异性87%。此外，该试验成功检测出33%（24例中有8例）的早期肿瘤。结论血浆表观遗传标志物可能对乳腺癌的检测有重要意义。在早期癌症中发现更多的乳腺癌特异性甲基化基因将改进这种方法。
PurposeNovel approaches to breast cancer screening are necessary, especially in the developing world where mammography is not feasible. In this study, we explored the hypothesis that blood-based biomarkers have potential for biomarkers for breast cancer.Patients and MethodsWe first determined the frequency of aberrant methylation of four candidate genes (APC, GSTP1, Rassf1A, and RAR beta 2) in primary breast cancer tissues from West African women with predominantly advanced cancers. We used a high-throughput DNA methylation assay (quantitative methylation-specific polymerase chain reaction) to examine plasma from 93 women with breast cancer and 76 controls for the presence of four methylated genes. Samples were randomly divided evenly into training and validation data sets. Cutoff values for gene positivity of the plasma-based assay and the gene panel were determined by receiver operating characteristic curves in the training data set and subsequently evaluated as a screening tool in the validation data set.ResultsMethylation of at least one gene resulted in a sensitivity of 62% and a specificity of 87%. Moreover, the assay successfully detected 33% (eight of 24) of early-stage tumors.ConclusionThese data suggest that epigenetic markers in plasma may be of interest for detection of breast cancer. Identification of additional breast cancer specific methylated genes with higher prevalence in early stage cancers would improve this approach.