title: Relationship of NKX3.1 and MYC gene copy number ratio and DNA hypomethylation to prostate carcinoma stage.
abstract: OBJECTIVE
  High stage prostate cancers have been reported to frequently harbor chromosome 8 alterations and hypomethylation of LINE-1 retrotransposons. The potential of these parameters for molecular staging of prostate carcinoma was investigated.
  
  
  METHODS
  High molecular weight DNA was extracted from 63 carcinoma tissues (22 pT2, 38 pT3, 3 pT4). Chromosome 8 alterations were followed by determining the ratio of NKX3.1 (at 8p21) to MYC (at 8q24) gene copy numbers (NKX3.1:MYC ratio) using a new real-time PCR technique. LINE-1 hypomethylation was quantified by Southern blot analysis.
  
  
  RESULTS
  In 42 carcinomas NKX3.1 copy numbers were altered, with decreases in 32 cases. Copy numbers of MYC were increased in 38 cases and diminished in four. The NKX3.1:MYC ratio was altered in 45 specimens, with a decrease in all but two. NKX3.1 loss was associated with tumor stage (p<0.03) and MYC gain with Gleason score (p<0.03). The NKX3.1:MYC ratio was highly significantly associated with tumor stage (p<0.002), displaying 66% sensitivity and 87% specificity. LINE-1 hypomethylation was related (p<0.004) to tumor stage, but exhibited lower sensitivity (59%) and specificity (77%).
  
  
  CONCLUSIONS
  A straightforward PCR technique detecting chromosome 8 alterations might be useful to predict which prostate cancers are organ-confined while determination of hypomethylation appears to be somewhat less well suited.
authors.affiliation: Clinic of Urology and Pediatric Urology, University of the Saarland, Homburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Kindich
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Florl
authors.forename: Jörn
authors.initials: J
authors.lastname: Kamradt
authors.forename: Jan
authors.initials: J
authors.lastname: Lehmann
authors.forename: Mirko
authors.initials: M
authors.lastname: Müller
authors.forename: Bernd
authors.initials: B
authors.lastname: Wullich
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Schulz
mesh_terms: D000368:Aged; D019175:DNA Methylation; D016259:Genes, myc / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C491178:NKX3-1 protein, human; D014157:Transcription Factors