Methylation patterns in cell-free plasma DNA reflect removal of the primary tumor and drug treatment of breast cancer patients.
Methylation patterns in cell-free plasma DNA reflect removal of the primary tumor and drug treatment of breast cancer patients.
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DOI：
10.1002/ijc.25363
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发表时间：
2011-01-15
影响因子：
6.4
通讯作者：
Levenson, Victor V.
中科院分区：
文献类型：
--
作者：
Liggett, Thomas E.;Melnikov, Anatoliy A.;Marks, Jeffrey R.;Levenson, Victor V.
异常DNA甲基化是大多数类型癌症的特征，其反映在血浆中的无细胞循环DNA中。然而，手术切除肿瘤和随后的治疗是否会诱导血浆DNA甲基化的变化，这可用于监测治疗，这是未知的。在这项初步研究中，通过先前开发的MethDet-56技术确定了20名乳腺癌患者游离血浆DNA的甲基化。分析三个时间点的样本-手术前（基线），手术后（评估切除的效果）和手术后他莫昔芬治疗（确定治疗效果）。健康对照的甲基化模式用作所有比较的参考。在至少一次比较中，七个启动子发生了差异甲基化（p<0.05）;三个启动子在手术后发生了变化;另一个启动子在开始他莫昔芬治疗后发生了变化;四个启动子在基线与组合治疗样本中发生了差异甲基化。基线（术前）时PR PROX、MDGI、PAX 5和RARβ2甲基化的增加在联合治疗组中甲基化最低的健康对照组中减少。单纯手术降低了PAX 5和RARβ2的甲基化，而他莫昔芬治疗仅改变了ESR 1的B启动子的甲基化。手术和他莫昔芬治疗后，游离血浆DNA的甲基化模式发生变化，最显著的是联合治疗后。基线（手术前）模式变得与健康对照相似，表明无细胞血浆DNA中的甲基化模式可用于监测治疗。
Abnormal DNA methylation is a feature of most types of cancer, which is reflected in cell-free circulating DNA in plasma. It is, however, unknown whether surgical removal of the tumor and subsequent therapy induces changes in plasma DNA methylation, which can be used to monitor treatment. In this pilot study, methylation in cell-free plasma DNA of 20 breast cancer patients was determined by the previously developed MethDet-56 technique. Samples at three time points were analyzed – before surgery (baseline), after surgery (to evaluate the effects of resection), and after surgery on tamoxifen therapy (to determine the effects of treatment). Methylation patterns of healthy controls were used as a reference for all comparisons. Seven promoters were differentially methylated (p<0.05) in at least one comparison; three changed after surgery; another one changed after beginning of tamoxifen treatment; and four were differentially methylated in baseline vs. combined treatment samples. Increased methylation of PR PROX, MDGI, PAX 5, and RARβ2 at baseline (pre-surgery) diminished towards the healthy controls with the lowest methylation in the combined treatment group. Surgery alone decreased methylation in PAX 5 and RARβ2, while tamoxifen treatment changed methylation only in the B promoter of ESR1. Methylation patterns in cell-free plasma DNA change after surgery and tamoxifen treatment, most significantly – after combined treatment. The baseline (pre-surgery) patterns become similar to those of healthy controls, suggesting that methylation patterns in cell-free plasma DNA may be used to monitor treatment.
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