EPIGENETIC ALTERATIONS OF ADENOMATOUS POLYPOSIS COLI (APC), RETINOIC ACID RECEPTOR BETA (RARβ) AND SURVIVIN GENES IN TUMOR TISSUES AND VOIDED URINE OF BLADDER CANCER PATIENTS
EPIGENETIC ALTERATIONS OF ADENOMATOUS POLYPOSIS COLI (APC), RETINOIC ACID RECEPTOR BETA (RARβ) AND SURVIVIN GENES IN TUMOR TISSUES AND VOIDED URINE OF BLADDER CANCER PATIENTS
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DOI：
10.1170/204
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发表时间：
2012-01-01
影响因子：
1.6
通讯作者：
Attaleb, M.
中科院分区：
文献类型：
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作者：
Berrada, N.;Amzazi, S.;Attaleb, M.
据报道，CpG启动子甲基化在膀胱癌中频繁发生。此外，已证明从排尿中进行基因甲基化分析是可行的，并可以高度敏感地检测到。本研究的目的是确定APC、RARβ和Survivin基因甲基化模式在膀胱癌发生过程中的变化，并评估是否可以在尿沉渣中检测到DNA甲基化。应用MSP法检测32例膀胱癌患者肿瘤标本和尿沉渣DNA中这三种基因的启动子甲基化状态。肿瘤标本中APC、RARβ和Survivin基因甲基化频率分别为100%、75%和84.4%。APC基因甲基化在膀胱癌各病理分级和分期中均有表达。RARβ和Survivin基因启动子甲基化在高级别肿瘤中的发生率较高，且由低到高逐渐升高，但这两个基因启动子区甲基化与肿瘤分期/分级之间无明显相关性。为了探讨非侵袭性膀胱癌检测的临床应用价值，我们进一步分析了膀胱癌患者尿液中甲基化状态。大多数肿瘤组织中检测到的尿液标本DNA甲基化(93.7%)，APC、RARβ和Survivin的甲基化频率分别为79.3%、70.8%和96.3%。我们的结果表明APC、RARβ和Survivin基因启动子甲基化在膀胱癌中是常见的发现。甲基化标记不仅可以在膀胱组织中检测甲基化，还可以在尿沉渣中检测甲基化，这表明甲基化标记是一种很有前途的非侵入性膀胱癌检测工具。
The CpG promoter methylation has been reported to occur frequently in bladder cancer. Moreover, analysis of gene methylation has been shown to be feasible from voided urine and can be detected with a high degree of sensitivity. The aim of this present study is to determine how methylation patterns of APC, RAR beta and Survivin genes change during bladder carcinogenesis and to evaluate whether DNA methylation could be detected in urine sediment. Using the sensitive assay of MSP, we explored the promoter methylation status for the three genes in tumor specimens and urine sediment DNA from 32 bladder cancer patients. Methylation frequencies of the tested genes in tumor specimens were 100%, 75% and 84.4% for APC, RAR beta and Survivin, respectively. Hypermethylation of APC was found in all pathological grades and stages of bladder cancer. More frequent promoter hypermethylation of RAR beta and Survivin was observed in high grade tumors and the hypermethylation increased from low to high stages, but there was no significant correlation between stages/grades and hypermethylation of these two gene promoters. In order to investigate clinical usefulness for noninvasive bladder cancer detection, we further analyzed the methylation status in urine samples of bladder cancer patients. Methylation of the tested genes in urine sediment DNA was detected in the majority of cases that were hypermethylated in tumor samples (93.7%) and the frequencies were 79.3% 70.8% and 96.3% for APC, RAR beta and Survivin, respectively. Our results indicate that methylation of APC, RAR beta and Survivin gene promoters is a common finding in patients with bladder carcinoma. The ability to detect methylation not only in bladder tissue, but also in urine sediments, suggests that methylation markers are promising tools for noninvasive detection of bladder cancer.