Novel approaches for the early detection and management of prostate cancer are urgently needed. Adult sporadic cancers are known to arise through the accumulation of multiple clonal genetic alterations which can be used as targets for the detection of neoplastic cells in bodily fluids that surround or drain from an organ. Since the prostate is a gateway organ for urine passing from the bladder to urethra, we hypothesized that prostate cancer DNA might be present in urine. Using the sensitive methylation specific PCR we have established that a new molecular target, GSTP1 gene hypermethylation which is well established as """"""""early"""""""", frequent and cancer specific can be detected in a simple voided urine from patients with curable prostate cancer. We have demonstrated for the first time that molecular detection of prostate cancer in urine is feasible. Our specific objectives are; to determine the diagnostic utility of hypermethylation-based detection in urine from two clinically problematic populations, men with a persistently elevated PSA and negative biopsy and high risk men with a normal PSA, and to validate our initial findings of high specificity through a comprehensive approach to negative controls leading to the useful application of gene hypermethylation in prostate cancer diagnosis and management. Our long range goal is to make these molecular detection tests a clinical reality. We have preliminary evidence which indicates that a sensitive and specific molecular test providing diagnosis of prostate cancer is feasible from a simple urine specimen. We will test this further in two clinically problematic populations in need of better diagnosis.
| Ibragimova, Ilsiya; Ibáñez de Cáceres, Inmaculada; Hoffman, Amanda M et al. (2010) Global reactivation of epigenetically silenced genes in prostate cancer. Cancer Prev Res (Phila) 3:1084-92 |
