Methylation-specific sequencing of GSTP1 gene promoter in circulating/extracellular DNA from blood and urine of healthy donors and prostate cancer patients
Methylation-specific sequencing of GSTP1 gene promoter in circulating/extracellular DNA from blood and urine of healthy donors and prostate cancer patients
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DOI：
10.1196/annals.1448.039
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发表时间：
2008-01-01
期刊：
影响因子：
--
通讯作者：
Laktionov, Pavel P.
中科院分区：
文献类型：
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作者：
Bryzgunova, Olga E.;Morozkin, Evgeniy S.;Laktionov, Pavel P.
癌症相关基因的高甲基化启动子代表了基于人类血液和尿液中的循环/细胞外 DNA (cir/exDNA) 进行早期癌症诊断和监测的便捷靶点。由于靶DNA浓度低且CirDNA甲基化存在潜在多态性，血浆或尿液样本中甲基化抑癌基因的检测频率通常低于肿瘤组织样本。肿瘤抑制基因的甲基化 cir/exDNA 的测序提供了有关源自肿瘤细胞的 cirDNA 甲基化的信息，这对于优化癌症诊断是必要的。在这项工作中，通过对化学转化的 cir/exDNA 进行测序，我们研究了来自健康男性、前列腺癌 (PCa) 患者和良性前列腺增生 (BPH) 患者血液和尿液的 cir/exDNA 库中 GSTP1 基因启动子 (1001-1302, X08058) 的胞嘧啶甲基化谱。我们证明，cir/exDNA 甲基化的数据可以通过对血液和尿液中的 cir/exDNA 进行测序来获得。从每位患者的血浆、血细胞洗脱液和尿液中分离出的 DNA 具有相同的 GSTP1 基因甲基化谱。 PCa 患者细胞外 DNA 中 GSTP1 基因甲基化谱与健康供体和 BPH 患者的特征谱不同。
Hypermethylated promoters of cancer-related genes represent convenient targets for early cancer diagnosis and monitoring based on circulating/extracellular DNA (cir/exDNA) from human blood and urine. The frequency of detection of methylated tumor suppressor genes in plasma or urine samples is usually lower than in the samples of tumor tissue because of a low concentration of target DNA and potential polymorphism of cirDNA methylation. Sequencing of the methylated cir/exDNA of tumor suppression genes provides information about methylation of the cirDNA originating from the tumor cells, which is necessary for optimization of cancer diagnosis. In this work, by sequencing chemically converted cir/exDNA, we have studied the cytosine methylation profile of GSTP1 gene promoter (1001-1302, X08058) in the pool of cir/exDNA from the blood and urine of healthy men, prostate cancer (PCa) patients, and patients with benign prostatic hyperplasia (BPH). We demonstrated that the data on cir/exDNA methylation could be obtained from sequencing of the cir/exDNA from blood and urine. The DNA isolated from blood plasma and the eluates of blood cells and urine of each patient were characterized by the same methylation profile of the GSTP1 gene. The profile of GSTP1 gene methylation in the extracellular DNA of PCa patients differs from the profiles characteristic of healthy donors and patients with BPH.