|Reference : Development of urine-based DNA methylation assay for prostate cancer screening|
|Scientific congresses and symposiums : Poster|
|Life sciences : Biochemistry, biophysics & molecular biology|
Human health sciences : Oncology
Human health sciences : Urology & nephrology
|Development of urine-based DNA methylation assay for prostate cancer screening|
|Vener, T. I. [ > > ]|
|Derecho, C. [ > > ]|
|Varde, S. [ > > ]|
|Mazumder, A. [ > > ]|
|Groteclaes, Madeleine [ > > ]|
|Bierau, Katia [ > > ]|
|Louwagie, J. [ > > ]|
|Bigley, Joseph [ > > ]|
|de Leval, Laurence [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques - Département des sciences biomédicales et précliniques >]|
|Gaspar, Yves [ > > ]|
|Coppens, Luc [Université de Liège - ULg > > Urologie >]|
|de Leval, Jean [Université de Liège - ULg > Département des sciences cliniques > Département des sciences cliniques >]|
|Waltregny, David [Université de Liège - ULg > Département des sciences cliniques > Urologie - GIGA-R : Labo de recherche sur les métastases >]|
|98th annual meeting of the American Association for Cancer Research|
|14-18 avril 2007|
|American Association for Cancer Research|
|Los Angeles, CA|
|United States of America|
|[en] DNA ; bladder cancer ; methylation ; urine|
|[en] Introduction: The best outcome for patients with prostate cancer (PCa) is seen for those treated at an early stage of the disease. A digital rectal examination (DRE) and the measurement of serum prostate specific antigen (PSA) levels are the current standards for PCa early detection. However, serum PSA testing lacks both sensitivity and specificity, and core biopsies frequently fail to identify small foci of PCa. The availability of non-invasive diagnostic molecular tests that could allow for a more precise identification of malignant prostate cells in asymptomatic men would be of great clinical value to improve PCa diagnosis.
Study design: 114 men scheduled to undergo a prostate biopsy were enrolled in the study. The biopsies were triggered either by an abnormally high PSA value or by suspicious findings on DRE. Patients with other known or suspected urinary malignancy were excluded from the study. Morning, post-prostate massage and post-biopsy urine samples were collected from all individuals. The main goals of this study were a) to determine if prostate massage can improve the prostate DNA quantity compared to urine collected in the morning or after biopsy, and b) to evaluate the methylation status of a gene panel in urine samples from subjects with cancer found in prostate biopsy tissue cores versus subjects without cancer.
Methods: Gene promoter methylation is associated with prostate cancer and has been successfully used for the molecular detection of neoplasia in urine. We have developed real-time methylation specific PCR assays to define the methylation status of several genes.
Results: Median age of the patients was 65 years (range 48-85). PCa was found in 51% of the patients. Histological diagnosis of the biopsies was compared to methylation results in urine from 102 samples (89% success rate due low DNA yields for 12 samples). The comparison between different urine sampling techniques showed that prostate massage is needed. The best results were obtained in post massage urine samples with a combination of GSTP1, p14, p16, RARβ2 and RASSF1A resulting in a sensitivity of 74% and a specificity of 75%.
Future: A multiplex assay using the Cepheid SmartCycler™ II platform is under development. Further studies are in progress to validate the assay across multiple centers.
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