Reference : Identification and Validation of the Methylated TWIST1 and NID2 Genes through Real-Ti...
Scientific journals : Article
Human health sciences : Urology & nephrology
Human health sciences : Oncology
Identification and Validation of the Methylated TWIST1 and NID2 Genes through Real-Time Methylation-Specific Polymerase Chain Reaction Assays for the Noninvasive Detection of Primary Bladder Cancer in Urine Samples.
Renard, Isabelle [> > > >]
Joniau, Steven [> > > >]
van Cleynenbreugel, Ben [> > > >]
Collette, Catherine [ > > ]
Naome, Chistophe [> > > >]
Vlassenbroeck, Ilse [> > > >]
Nicolas, Hubert [ > > ]
de Leval, Jean mailto [Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques >]
Straub, Joseph [> > > >]
Van Criekinge, W. [> > > >]
Hamida, Wissem [> > > >]
Hellel, Majed [> > > >]
Thomas, Alexandre mailto [Centre Hospitalier Universitaire de Liège - CHU > > Urologie >]
De Leval, Laurence mailto [Centre Hospitalier Universitaire de Liège - CHU > > Anatomie pathologique >]
Bierau, Katia [> > > >]
Waltregny, David mailto [Université de Liège - ULiège > Département des sciences cliniques > Urologie - GIGA-R : Labo de recherche sur les métastases >]
European Urology
[en] methylation ; bladder ; cancer
[en] BACKGROUND: Accumulating evidence suggests that DNA methylation markers could serve as sensitive and specific cancer biomarkers. OBJECTIVE: To determine whether a panel of methylated genes would have the potential to identify primary bladder cancer (BCa) in voided urine samples. DESIGN, SETTING, AND PARTICIPANTS: A pharmacologic unmasking reexpression analysis in BCa cell lines was initially undertaken to unveil candidate methylated genes, which were then evaluated in methylation-specific polymerase chain reaction (MSP) assays performed on DNA extracted from noncancerous and cancerous bladder tissues. The most frequently methylated genes in cancerous tissues, with 100% specificity, were retained for subsequent MSP analysis in DNA extracted from urine samples to build and validate a panel of potential methylated gene markers. Urine samples were prospectively collected at three urologic centres from patients with histologically proven BCa and processed for use in real-time MSP and cytologic analysis. Patients with nonmalignant urologic disorders were included as controls. MEASUREMENTS: A urine sample was classified as valid when >/=10 copies of the gene encoding ss-actin were measured in the urine sediment genomic DNA. Sensitivity, specificity, and predictive values of the MSP and cytology tests were assessed and compared. RESULTS AND LIMITATIONS: MSP assays performed on 466 of the 496 (94%) valid urine samples identified two genes, TWIST1 and NID2, that were frequently methylated in urine samples collected from BCa patients, including those with early-stage and low-grade disease. The sensitivity of this two-gene panel (90%) was significantly better than that of cytology (48%), with comparable specificity (93% and 96%, respectively). The positive predictive value and negative predictive value of the two-gene panel was 86% and 95%, respectively. CONCLUSIONS: Detection of the methylated TWIST1 and NID2 genes in urine sediments using MSP provides a highly (>/=90%) sensitive and specific, noninvasive approach for detecting primary BCa. TRIAL REGISTRATION: BlCa-001 study - EudraCt 2006-003303-40.
Service d'Urologie
Researchers ; Professionals

File(s) associated to this reference

Fulltext file(s):

Restricted access
Pub#62 Methylation Bladder cancer Eur Urol 2009.pdfPublisher postprint585.86 kBRequest copy

Bookmark and Share SFX Query

All documents in ORBi are protected by a user license.