Quantitation of Promoter Methylation of Multiple Genes in Urine DNA and Bladder Cancer Detection

作者：Mohammad Obaidul Hoque, Shahnaz Begum, Özlem Topaloglu, Aditi Chatterjee, Eli Rosenbaum, Wim Van Criekinge, William H. Westra, Mark Schoenberg, MARIANNA L. ZAHURAK, Steven N. Goodman, David Sidransky · 发表于：JNCI Journal of the National Cancer Institute · 年份：2006 · DOI：10.1093/jnci/djj265 · 被引用次数：268 · 研究领域：Epigenetics and DNA Methylation、Bladder and Urothelial Cancer Treatments、Ferroptosis and cancer prognosis

BACKGROUND: The noninvasive identification of bladder tumors may improve disease control and prevent disease progression. Aberrant promoter methylation (i.e., hypermethylation) is a major mechanism for silencing tumor suppressor genes and other cancer-associated genes in many human cancers, including bladder cancer. METHODS: A quantitative fluorogenic real-time polymerase chain reaction (PCR) assay was used to examine primary tumor DNA and urine sediment DNA from 15 patients with bladder cancer and 25 control subjects for promoter hypermethylation of nine genes (APC, ARF, CDH1, GSTP1, MGMT, CDKN2A, RARbeta2, RASSF1A, and TIMP3) to identify potential biomarkers for bladder cancer. We then used these markers to examine urine sediment DNA samples from an additional 160 patients with bladder cancers of various stages and grades and from an additional 69 age-matched control subjects. Data were analyzed on the basis of a prediction model and were internally validated using a jacknife procedure. All statistical tests were two-sided. RESULTS: For all 15 patients with paired DNA samples, the promoter methylation pattern in urine matched that in the primary tumors. Four genes displayed 100% specificity. Of the 175 bladder cancer patients, 121 (69%, 95% confidence interval [CI] = 62% to 76%) displayed promoter methylation in at least one of these genes (CDKN2A, ARF, MGMT, and GSTP1), whereas all control subjects were negative for such methylation (100% specificity, 95% CI = 96% to 100%)...