Genome-wide DNA methylation profiles in urothelial carcinomas and urothelia at the precancerous stage
Genome-wide DNA methylation profiles in urothelial carcinomas and urothelia at the precancerous stage
复制标题
DOI：
10.1111/j.1349-7006.2009.01330.x
复制
发表时间：
2010-01-01
期刊：
影响因子：
5.7
通讯作者：
Kanai, Yae
中科院分区：
文献类型：
--
作者：
Nishiyama, Naotaka;Arai, Eri;Kanai, Yae
为了阐明多阶段尿路上皮癌发生过程中的全基因组DNA甲基化谱，在18例来自非尿路上皮癌（UC）患者的正常尿路上皮（C）、17例来自UC患者的非癌性尿路上皮（N）和40例UC中进行了基于细菌人工染色体（BAC）阵列的甲基化CpG岛扩增（BAMCA）。与C相比，甚至在N中也观察到多个BAC克隆上的DNA低甲基化和高甲基化。主成分分析显示从C到N和UC的DNA甲基化进行性改变。从侵袭性UC患者获得的N中的DNA甲基化谱由侵袭性UC自身遗传，即N中的DNA甲基化改变与更恶性UC的发展相关。通过Wilcoxon检验选择的83个BAC克隆上的DNA甲基化状态的组合能够完全区分N和C，并且诊断N具有高致癌风险，具有100%的灵敏度和特异性。通过Wilcoxon检验选择的20个BAC克隆的DNA甲基化状态的组合能够完全区分手术后复发的患者和没有复发的患者。通过Wilcoxon检验选择的11个BAC克隆的DNA甲基化状态的组合能够完全区分患有膀胱内异时性UC发展的肾盂或输尿管UC的患者与没有发展的患者。DNA甲基化的全基因组改变可能参与了从癌前阶段到UC的尿路上皮癌的发生，DNA甲基化谱可能为致癌风险估计和预测提供最佳指标。（Cancer Sci 2009）。
To clarify genome-wide DNA methylation profiles during multistage urothelial carcinogenesis, bacterial artificial chromosome (BAC) array-based methylated CpG island amplification (BAMCA) was performed in 18 normal urothelia obtained from patients without urothelial carcinomas (UCs) (C), 17 noncancerous urothelia obtained from patients with UCs (N), and 40 UCs. DNA hypo- and hypermethylation on multiple BAC clones was observed even in N compared to C. Principal component analysis revealed progressive DNA methylation alterations from C to N, and to UCs. DNA methylation profiles in N obtained from patients with invasive UCs were inherited by the invasive UCs themselves, that is DNA methylation alterations in N were correlated with the development of more malignant UCs. The combination of DNA methylation status on 83 BAC clones selected by Wilcoxon test was able to completely discriminate N from C, and diagnose N as having a high risk of carcinogenesis, with 100% sensitivity and specificity. The combination of DNA methylation status on 20 BAC clones selected by Wilcoxon test was able to completely discriminate patients who suffered from recurrence after surgery from patients who did not. The combination of DNA methylation status for 11 BAC clones selected by Wilcoxon test was able to completely discriminate patients with UCs of the renal pelvis or ureter who suffered from intravesical metachronous UC development from patients who did not. Genome-wide alterations of DNA methylation may participate in urothelial carcinogenesis from the precancerous stage to UC, and DNA methylation profiling may provide optimal indicators for carcinogenetic risk estimation and prognostication. (Cancer Sci 2009).