title: Promoter hypermethylation in circulating blood cells identifies prostate cancer progression.
abstract: Promoter hypermethylation of circulating cell DNA has been advocated as a diagnostic marker for prostate cancer, but its prognostic use is currently unclear. To assess this role, we compared hypermethylation of circulating cell DNA from prostate cancer patients with (Group 1, n = 20) and without (Group 2, n = 22) disease progression and age-matched controls (benign prostatic hyperplasia, Group 3, n = 22). We measured hypermethylation of 10 gene promoters in 2 sequential venous samples, obtained at diagnosis and during disease progression (median time, 15 months later). Matched time samples were obtained in the nonprogressing patients. We found that more hypermethylation was detected in the diagnostic sample from the patients with cancer than in controls for GSTP1, RASSF1 alpha, APC and RAR beta (p < 0.0001). Patients undergoing disease progression had a significant increase in methylation levels of these 4 genes when compared to the other patients (p < 0.001). Patients at risk of disease progression have higher detectable concentrations of circulating cell hypermethylation, than those without progression. The extent of this hypermethylation increases during disease progression and can be used to identify the extent and duration of treatment response in prostate cancer.
authors.affiliation: Institute for Cancer Studies, University of Sheffield, Royal Hallamshire Hospital, Sheffield, United Kingdom. morgan.roupret@psl.aphp.fr
authors.forename: Morgan
authors.initials: M
authors.lastname: Rouprêt
authors.forename: Vincent
authors.initials: V
authors.lastname: Hupertan
authors.forename: James W F
authors.initials: JW
authors.lastname: Catto
authors.forename: David R
authors.initials: DR
authors.lastname: Yates
authors.forename: Ishtiaq
authors.initials: I
authors.lastname: Rehman
authors.forename: Laura M
authors.initials: LM
authors.lastname: Proctor
authors.forename: Joshua
authors.initials: J
authors.lastname: Phillips
authors.forename: Mark
authors.initials: M
authors.lastname: Meuth
authors.forename: Olivier
authors.initials: O
authors.lastname: Cussenot
authors.forename: Freddie C
authors.initials: FC
authors.lastname: Hamdy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D019175:DNA Methylation; D018450:Disease Progression; D017491:Genes, APC / Q000502:physiology; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000097:blood* / Q000235:genetics* / Q000628:therapy; D018168:Receptors, Retinoic Acid / Q000235:genetics; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C411762:RASSF1 protein, human; D018168:Receptors, Retinoic Acid; D025521:Tumor Suppressor Proteins; C082925:retinoic acid receptor beta; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi