Hypermethylation of Multiple Genes in Tumor Tissues and Voided Urine in Urinary Bladder Cancer Patients

Purpose: We aimed to investigate the methylation pattern in bladder cancer and assess the diagnostic potential of such epigenetic changes in urine. Experimental Design: The methylation status of 7 genes ( RAR β , DAPK, E-cadherin , p16, p15, GSTP1 , and MGMT) in 98 cases of bladder transitional cell...

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Published in:	Clinical cancer research Vol. 8; no. 2; pp. 464 - 470
Main Authors:	CHAN, Michael W. Y, CHAN, Lun W, TO, Ka F, TANG, Nelson L. S, TONG, Joanna H. M, LO, Kwok W, LEE, Tin L, Y.CHEUNG, Ho, WONG, Wai S, CHAN, Peter S. F, LAI, Fernand M. M
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA American Association for Cancer Research 01-02-2002
Subjects:	Adult Aged Aged, 80 and over Apoptosis Regulatory Proteins Biological and medical sciences Cadherins - genetics Cadherins - metabolism Cadherins - urine Calcium-Calmodulin-Dependent Protein Kinases - genetics Calcium-Calmodulin-Dependent Protein Kinases - metabolism Calcium-Calmodulin-Dependent Protein Kinases - urine Carcinoma, Transitional Cell - genetics Carcinoma, Transitional Cell - metabolism Carcinoma, Transitional Cell - urine Cyclin-Dependent Kinase Inhibitor p16 - metabolism Death-Associated Protein Kinases DNA Methylation Female Humans Male Medical sciences Middle Aged Nephrology. Urinary tract diseases Receptors, Retinoic Acid - genetics Receptors, Retinoic Acid - metabolism Sensitivity and Specificity Tumors of the urinary system Urinary Bladder Neoplasms - genetics Urinary Bladder Neoplasms - metabolism Urinary Bladder Neoplasms - urine Urinary tract. Prostate gland Human Urine Urinary system disease Nucleotide sequence Transcription promoter Tumoral tissue Urinary tract disease Transitional cell carcinoma Malignant tumor In vitro Gene silencing Sensitivity Gene GC rich sequence Urinary bladder DNA Bladder disease Methylation Comparative study
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Summary:	Purpose: We aimed to investigate the methylation pattern in bladder cancer and assess the diagnostic potential of such epigenetic changes in urine. Experimental Design: The methylation status of 7 genes ( RAR β , DAPK, E-cadherin , p16, p15, GSTP1 , and MGMT) in 98 cases of bladder transitional cell carcinoma and 4 cases of carcinoma in situ was analyzed by methylation-specific PCR. Twenty-two cases had paired voided urine samples for analysis. Results: In transitional cell carcinoma tumor tissues, aberrant methylation was frequently detected in RAR β (87.8%), DAPK (58.2%), E-cadherin (63.3%), and p16 (26.5%), whereas methylation of p15 (13.3%), GSTP1 (5.1%), and MGMT (5.1%) is not common. No association between methylation status and grading or muscle invasiveness was demonstrated. In 22 paired voided urine samples of bladder cancer, methylation of DAPK, RAR β , E-cadherin , and p16 could be detected in 45.5%, 68.2%, 59.1%, and 13.6% of the cases, respectively. The sensitivity of methylation analysis (90.9%) was higher than that of urine cytology (45.5%) for cancer detection. Methylation of RAR β (50%), DAPK (75%), and E-cadherin (50%) was also detected in carcinoma in situ . In 7 normal urothelium samples and 17 normal urine controls, no aberrant methylation was detected except for RAR β methylation in 3 normal urothelium samples (42.9%) and 4 normal urine samples (23.5%), respectively. Conclusions: Our results demonstrated a distinct methylation pattern in bladder cancer with frequent methylation of RAR β , DAPK, E-cadherin , and p16 . Detection of gene methylation in routine voided urine using selected markers appeared to be more sensitive than conventional urine cytology.
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ISSN:	1078-0432 1557-3265