This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yu, J. Articles by Zhu, J. Search for Related Content PubMed PubMed Citation Articles by Yu, J. Articles by Zhu, J.

A Novel Set of DNA Methylation Markers in Urine Sediments for Sensitive/Specific Detection of Bladder Cancer

Authors' Affiliations: ¹ Cancer Genetics and Gene Therapy Program, The State Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute and ² Epigenomics Program, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University; ³ Department of Urology, Zhongshan Hospital Affiliated to Fudan University; ⁴ Bioinformation Center of Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; ⁵ Guangxi Cancer Hospital, Nanning, Guangxi, China; ⁶ Division of Cellular Dynamics, Hefei National Laboratory and University of Science and Technology of China, Hefei, China; ⁷ Department of Physiology and Cancer Biology Program, Morehouse School of Medicine, Atlanta, Georgia; and ⁸ School of Life Sciences, Zhejiang Science and Technology University, Hangzhou, Zhejiang, China

Requests for reprints: Jingde Zhu, Shanghai Cancer Institute, Shanghai, China. Phone/Fax: 86-21-64224285; E-mail: zhujingde{at}yahoo.com; Xuebiao Yao, University of Science & Technology, Hefel, China. Phone/Fax: 86-551-3606304; E-mail: yaoxb{at}ustc.edu.com.

Purpose: This study aims to provide a better set of DNA methylation markers in urine sediments for sensitive and specific detection of bladder cancer.

Experimental Design: Fifty-nine tumor-associated genes were profiled in three bladder cancer cell lines, a small cohort of cancer biopsies and urine sediments by methylation-specific PCR. Twenty-one candidate genes were then profiled in urine sediments from 132 bladder cancer patients (8 cases for stage 0a; 68 cases for stage I; 50 cases for stage II; 4 cases for stages III; and 2 cases for stage IV), 23 age-matched patients with noncancerous urinary lesions, 6 neurologic diseases, and 7 healthy volunteers.

Results: Despite six incidences of four genes reported in 3 of 23 noncancerous urinary lesion patients analyzed, cancer-specific hypermethylation in urine sediments were reported for 15 genes (P < 0.05). Methylation assessment of an 11-gene set (SALL3, CFTR, ABCC6, HPR1, RASSF1A, MT1A, RUNX3, ITGA4, BCL2, ALX4, MYOD1, DRM, CDH13, BMP3B, CCNA1, RPRM, MINT1, and BRCA1) confirmed the existing diagnosis of 121 among 132 bladder cancer cases (sensitivity, 91.7%) with 87% accuracy. Significantly, more than 75% of stage 0a and 88% of stage I disease were detected, indicating its value in the early diagnosis of bladder cancer. Interestingly, the cluster of reported methylation markers used in the U.S. bladder cancers is distinctly different from that identified in this study, suggesting a possible epigenetic disparity between the American and Chinese cases.

Conclusions: Methylation profiling of an 11-gene set in urine sediments provides a sensitive and specific detection of bladder cancer.

This article has been cited by other articles:

				K.L. Greathouse, J.D. Cook, K. Lin, B.J. Davis, T.D. Berry, T.G. Bredfeldt, and C.L. Walker Identification of Uterine Leiomyoma Genes Developmentally Reprogrammed by Neonatal Exposure to Diethylstilbestrol Reproductive Sciences, October 1, 2008; 15(8): 765 - 778. [Abstract] [PDF]

				K.C. A. Chan, S. F. Leung, S. W. Yeung, A. T.C. Chan, and Y.M. D. Lo Quantitative Analysis of the Transrenal Excretion of Circulating EBV DNA in Nasopharyngeal Carcinoma Patients Clin. Cancer Res., August 1, 2008; 14(15): 4809 - 4813. [Abstract] [Full Text] [PDF]