title: A DNA hypermethylation profile reveals new potential biomarkers for prostate cancer diagnosis and prognosis.
abstract: BACKGROUND
  DNA hypermethylation has emerged as a novel molecular biomarker for the evaluation of prostate cancer diagnosis and prognosis. Defining the specific gene hypermethylation profile for prostate cancer could involve groups of genes that specifically discriminate patients with indolent and aggressive tumors.
  
  
  METHODS
  Genome-wide methylation analysis was performed on 83 tumor and 10 normal prostate samples using the GoldenGate Methylation Cancer Panel I (Illumina, Inc.). All clinical stages of disease were considered.
  
  
  RESULTS
  We found 41 genes hypermethylated in more than 20% of the tumors analyzed (P < 0.01). Of these, we newly identified GSTM2 and PENK as being genes that are hypermethylated in prostate cancer and that were simultaneously methylated in 40.9% of the tumors analyzed. We also identified panels of genes that are more frequently methylated in tumor samples with clinico-pathological indicators of poor prognosis: a high Gleason score, elevated Ki-67, and advanced disease. Of these, we found simultaneous hypermethylation of CFTR and HTR1B to be common in patients with a high Gleason score and high Ki-67 levels; this might indicate the population at higher risk of therapeutic failure. The DNA hypermethylation profile was associated with cancer-specific mortality (log-rank test, P = 0.007) and biochemical recurrence-free survival (log-rank test, P = 0.0008).
  
  
  CONCLUSIONS
  Our findings strongly indicate that epigenetic silencing of GSTM2 and PENK is a common event in prostate cancer that could be used as a molecular marker for prostate cancer diagnosis. In addition, simultaneous HTR1B and CFTR hypermethylation could help discriminate aggressive from indolent prostate tumors.
authors: Departamento de Biología de Sistemas, Unidad Docente de Bioquímica y Biología Molecular, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
authors: Nadia
authors: N
authors: Ashour
authors: Javier C
authors: JC
authors: Angulo
authors: Guillermo
authors: G
authors: Andrés
authors: Raúl
authors: R
authors: Alelú
authors: Ana
authors: A
authors: González-Corpas
authors: María V
authors: MV
authors: Toledo
authors: José M
authors: JM
authors: Rodríguez-Barbero
authors: Jose I
authors: JI
authors: López
authors: Manuel
authors: M
authors: Sánchez-Chapado
authors: Santiago
authors: S
authors: Ropero
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016172:DNA Fingerprinting / Q000379:methods*; D019175:DNA Methylation / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D012189:Retrospective Studies; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor
keywords: DNA methylation; Ki-67; biochemical progression; biomarkers; disease-specific survival; prostate cancer