CpG island hypermethylation of cell-free circulating serum DNA in patients with testicular cancer.
OBJECTIVE
DNA hypermethylation is a common cancer associated alteration. We analyzed methylation patterns of cell-free serum DNA in patients with testicular cancer.


METHODS
Hypermethylation at APC, GSTP1, PTGS2, p14(ARF), p16(INK) and RASSF1A was analyzed using real-time polymerase chain reaction following methylation sensitive restriction endonuclease treatment in 73 patients with testicular cancer and 35 healthy individuals.


RESULTS
Hypermethylation was more common in patients with testicular cancer than in healthy individuals, including APC 57% and 6%, p16(INK) 53% and 17%, p14(ARF) 53% and 0%, RASSF1A 47% and 0%, PTGS2 45% and 0%, and GSTP1 25% and 0%, respectively (each p <0.01). Methylation frequencies at the investigated gene sites were similar in nonseminoma and seminoma cases (p >0.05). Diagnostic information was increased when multiple gene sites were analyzed in combination (ROC AUC 0.834, 67% sensitivity and 97% specificity). Diagnostic information was superior to the analysis of AFP/HCG/PLAP/LDH (combined sensitivity 58% and AUC 0.791). The sensitivity of hypermethylation in patients with unsuspicious conventional tumor markers was 71% (AUC 0.871, 97% specificity). Hypermethylation at PTGS2 was more common in patients with pT1 stage tumors (p = 0.011).


CONCLUSIONS
The detection of hypermethylated cell-free serum DNA has the potential of a useful additional diagnostic parameter in patients with testicular germ cell cancer. Furthermore, in cases without conventional tumor marker increases testing CpG island hypermethylation in cell-free circulation DNA may improve the ability to detect early and/or recurrent testicular cancer.
Ellinger
Jörg
J
Klinik und Poliklinik für Urologie and Institut für Pathologie, Universitätsklinikum Bonn, Bonn, Germany. joerg.ellinger@ukb.uni-bonn.de
Albers
Peter
P
Perabo
Frank G
FG
Müller
Stefan C
SC
von Ruecker
Alexander
A
Bastian
Patrick J
PJ
D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D001707:Biopsy, Needle; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D018899:CpG Islands / Q000235:genetics*; D004247:DNA / Q000097:blood; D019175:DNA Methylation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009373:Neoplasms, Germ Cell and Embryonal / Q000097:blood* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D009919:Orchiectomy / Q000379:methods; D011336:Probability; D011379:Prognosis; D012372:ROC Curve; D012016:Reference Values; D012680:Sensitivity and Specificity; D013736:Testicular Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D055815:Young Adult
D014408:Biomarkers, Tumor; D004247:DNA