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.
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.
Authors: Dora Markulin; Aleksandar Vojta; Ivana Samaržija; Marija Gamulin; Ivona Bečeheli; Irena Jukić; Čedomir Maglov; Vlatka Zoldoš; Aleksandra Fučić Journal: Cancer Genomics Proteomics Date: 2017 Sep-Oct Impact factor: 4.069
Authors: Stefan Hauser; Annette Kaminski; Isabella Syring; Stefan Holdenrieder; Klaus-Peter Dieckmann; Stefan C Muller; Jorg Ellinger Journal: In Vivo Date: 2019 Nov-Dec Impact factor: 2.155