Relationship of NKX3.1 and MYC gene copy number ratio and DNA hypomethylation to prostate carcinoma stage.
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.
Kindich
Roland
R
Clinic of Urology and Pediatric Urology, University of the Saarland, Homburg, Germany.
Florl
Andrea R
AR
Kamradt
Jörn
J
Lehmann
Jan
J
Müller
Mirko
M
Wullich
Bernd
B
Schulz
Wolfgang A
WA
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*
D018398:Homeodomain Proteins; C491178:NKX3-1 protein, human; D014157:Transcription Factors