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J Urol. 2009 Jul;182(1):324-9. doi: 10.1016/j.juro.2009.02.106. Epub 2009 May 17.

CpG island hypermethylation of cell-free circulating serum DNA in patients with testicular cancer.

Author information

1
Klinik und Poliklinik für Urologie and Institut für Pathologie, Universitätsklinikum Bonn, Bonn, Germany. joerg.ellinger@ukb.uni-bonn.de

Abstract

PURPOSE:

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

MATERIALS AND 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.

PMID:
19447423
DOI:
10.1016/j.juro.2009.02.106
[Indexed for MEDLINE]

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