title: Discovery and validation of 3 novel DNA methylation markers of prostate cancer prognosis.
abstract: OBJECTIVE
  About 15% of men experience prostate specific antigen recurrence after radical prostatectomy. A DNA methylation based molecular test could provide important information to predict which patients are most likely to experience recurrence.
  
  
  METHODS
  We performed a genome-wide scan to find aberrantly methylated loci in prostate cancer from patients with early recurrence, high Gleason score or advanced stage. We discovered 441 candidate methylation markers and further analyzed 62 candidates in a methylation microarray study of 304 frozen prostatectomy samples.
  
  
  RESULTS
  Methylation of 25 markers was significantly changed in high Gleason score (8-10) vs low Gleason score (2-6) cancers. Methylation levels of the 3 marker candidates GPR7, ABHD9 and an expressed sequence tag on chromosome 3 (Chr3-EST) were significantly increased in patients who did vs did not experience early PSA recurrence (Bonferroni correction p<0.05). Furthermore, these markers were also informative when the sample set was restricted to 68 mid range Gleason score (6 or 7) samples only. We developed real-time polymerase chain reaction assays for ABHD9 and Chr3-EST, and measured methylation in paraffin embedded, formalin fixed prostatectomy samples from an independent set of 223 patients. Methylation of the 2 markers was significantly higher in patients with early PSA recurrence compared to that in patients who did not experience PSA recurrence.
  
  
  CONCLUSIONS
  We report that methylation of the 3 novel markers GPR7, ABHD9 and Chr3-EST is significantly associated with prostate cancer prognosis. Incorporation of these methylation markers into clinical practice will result in more accurate prediction of which patients are likely to experience PSA recurrence.
authors: Epigenomics, Inc., Seattle, Washington, USA.
authors: Susan
authors: S
authors: Cottrell
authors: Klaus
authors: K
authors: Jung
authors: Glen
authors: G
authors: Kristiansen
authors: Elke
authors: E
authors: Eltze
authors: Axel
authors: A
authors: Semjonow
authors: Michael
authors: M
authors: Ittmann
authors: Arndt
authors: A
authors: Hartmann
authors: Thomas
authors: T
authors: Stamey
authors: Carolina
authors: C
authors: Haefliger
authors: Gunter
authors: G
authors: Weiss
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D020224:Expressed Sequence Tags; D005500:Follow-Up Studies; D019204:GTP-Binding Proteins; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D018013:Receptors, Neuropeptide / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C485722:NPBWR1 protein, human; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D017430:Prostate-Specific Antigen; D019204:GTP-Binding Proteins