title: Inverse association of p16 INK4a and p14 ARF methylation of the CDKN2a locus in different Gleason scores of prostate cancer.
abstract: BACKGROUND
  Promoter hypermethylation is an important epigenetic mechanism in the regulation of several key modulators of prostate carcinoma progression. Recent studies suggest that the polycomb-group (PcG) protein BMI1 may have an impact on epigenetic regulation of several targets, including the CDKN2a locus.
  
  
  METHODS
  In this study, we investigated the association of BMI1 expression, promoter methylation of CDKN2a (p16(INK4a) and p14(ARF)) and TMS1 with pathological variables (Gleason score, TNM stage, perineural invasion) in prostate cancer (PCa).
  
  
  RESULTS
  Methylation of p16(INK4a) and p14(ARF) revealed an inverse association with Gleason score 7b and Gleason score 6. No significant association could be demonstrated for BMI1 -overexpression and promoter methylation of p16(INK4a), p14(ARF) and TMS1 as well as pT category.
  
  
  CONCLUSIONS
  Our data suggest that the CDKN2a locus is a switch in PCa with methylation of p16(INK4a) being a marker for more aggressive tumours of Gleason score 7b, but no association with BMI overexpression was observed.
authors.affiliation: Institute of Pathology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Verdoodt
authors.forename: F
authors.initials: F
authors.lastname: Sommerer
authors.forename: R-J
authors.initials: RJ
authors.lastname: Palisaar
authors.forename: J
authors.initials: J
authors.lastname: Noldus
authors.forename: M
authors.initials: M
authors.lastname: Vogt
authors.forename: S
authors.initials: S
authors.lastname: Nambiar
authors.forename: A
authors.initials: A
authors.lastname: Tannapfel
authors.forename: A
authors.initials: A
authors.lastname: Mirmohammadsadegh
authors.forename: M
authors.initials: M
authors.lastname: Neid
mesh_terms: D000368:Aged; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D015870:Gene Expression; D056426:Genetic Loci; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D063150:Polycomb Repressive Complex 1; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics*
chemical_list: C069077:BMI1 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D025803:Tumor Suppressor Protein p14ARF; D063150:Polycomb Repressive Complex 1