Abstract
Abstract Changes in DNA methylation of crucial cancer genes including tumor suppressors can occur early in carcinogenesis, being potentially important early indicators of cancer. The objective of this study was to examine a multiplexed approach to assess the methylation of tumor suppressor genes as urinary diagnostic markers for bladder cancer. A multicandidate probe panel interrogated DNA for aberrant methylation status in 25 tumor suppressor genes using a methylation-specific multiplex ligation-dependent probe amplification assay (MS-MLPA). Initial analyses in bladder cancer cell lines (n=14), and fresh-frozen primary bladder tumor specimens (n=31) supported the panel of genes selected to be altered in bladder cancer. MS-MLPA was then optimized for its application in body fluids using two sets of urinary specimens (n=146) including bladder cancer patients (n=96) and controls (n=50). Genes previously reported to be methylated such as BRCA1, CDH13 and RARB, were confirmed to be methylated in the three types of samples analyzed. WT1 and PAX5A were identified as novel tumor suppressor candidates methylated in bladder cancer specimens. The most frequently methylated genes in the bladder tumors analyzed were BRCA1 (71.0%), WT1 (38.7%), and RARB (38.7%), being WT1 methylation significantly associated with tumor stage (p=0.011). BRCA1, WT1 and RARB were also as the most frequently methylated genes in two independent training and validation sets of urinary specimens (n=146). ROC curves analyses revealed significant diagnostic accuracies over 70% in both sets of urinary specimens for BRCA1, RARB, WT1, PAX5A and CDH13. In summary, the novelty of this report deals with applying a multiplexed methylation technique for bladder cancer, and also in body fluids. MS-MLPA represents a promising methylation profiling tool for histopathologic stratification of bladder tumors, and diagnosis using urinary samples. This latter is clinically relevant by offering a non-invasive strategy for the clinical management of patients affected with uroepithelial neoplasias Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4685.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
