Naslov
Methylation levels of MGMT and RASSF1 genes in testicular cancer as potential biomarkers for the success of chemotherapy

Autori
Gamulin, Marija ; Zoldoš, Vlatka ; Bečeheli, Ivona ; Markulin, Dora ; Samaržija, Ivana ; Vojta, Aleksandar ; Grgić, Mislav ; Jukić, Irena ; Maglov, Čedomir ; Žunec, Renata ; Aleksandra, Fučić

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Skup
2015 ASCO Annual Meeting

Mjesto i datum
Chicago (IL), Sjedinjene Američke Države, 25.05.2015. - 02.06.2015

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
testicular cancer, methylation

Sažetak
Background: Since testicular cancer shows different disease progress depending on etiology and the neoplastic tissue profile, with epigenetic changes being a likely underlying mechanism, we investigated CpG methylation of MGMT and RASSF1, which had been identified as promising candidate biomarkers for disease progression, chemotherapy success and prognosis. Methods: Genomic DNA was isolated from blood of 32 healthy individuals and 32 patients with testicular cancer before and after the chemotherapy: etoposide, cisplatin, bleomycin (BEP). Eighteen samples were seminomas and 14 were nonseminomas. For quantitative measurement of DNA methylation levels in MGMT and RASSF1A, bisulfite-converted DNA was amplified by PCR and then sequenced using a pyrosequencing technology. Results: Methylation levels were not significantly different for MGMT before and after chemotherapy ; however, methylation of the tested CpG sites in RASSF1 was significantly higher in patients before treatment compared with controls at 5 of 9 sites, two sites remaining significant even after the Bonferroni correction. Methylation of RASSF1 approached that of the controls after treatment. In addition, we found indications that additional stratification by histopathological profile might add value to MGMT and RASSF1 methylation as a prognostic marker. The methylation of LINE1 elements was similar in patients before and after chemotherapy. Conclusions: Increasing statistical power by studying larger cohorts has a potential to further confirm RASSF1 methylation as a chemotherapy success biomarker, while additional stratification by histopahological characteristics could give further insight leading to more accurate prognosis using both RASSF1 and MGMT, thereby enabling better risk- adapted management of testicular cancer.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA