Markulin Dora, Vojta Aleksandar, Samaržija Ivana, Gamulin Marija, Bečeheli Ivona, Jukić Irena, Maglov Čedomir, Zoldoš Vlatka, Fučić Aleksandra
University of Zagreb, Faculty of Science, Department of Biology, Division of Molecular Biology, Zagreb, Croatia.
University Hospital Centre Zagreb, Department of Oncology, Zagreb, Croatia.
Cancer Genomics Proteomics. 2017 Sep-Oct;14(5):363-372. doi: 10.21873/cgp.20046.
The RAS association domain family protein 1a (RASSF1A) is a prominent tumor suppressor gene showing altered promoter methylation in testicular germ cell tumors (TGCT). RASSF1A promoter hypermethylation might represent an early event in TGCT tumorigenesis. We investigated whether the RASSF1A promoter methylation in peripheral blood of TGCT patients can be associated with testicular cancer risk.
Following a meta-analysis, we performed a cohort study including 32 testicular cancer patients and 32 healthy controls. Promoter methylation of the RASSF1A and O-methylguanine-DNA-methyltransferase (MGMT) genes was analyzed using bisulfite pyrosequencing of DNA from peripheral blood.
Meta-analysis showed an odds ratio (OR) of 7.69 for RASSF1A promoter methylation as a risk factor for TGCT. Cohort study found altered methylation of the RASSF1A promoter in blood of TGCT patients. Methylation was higher in TGCT patients before BEP chemotherapy.
The meta-analysis indicates a role of the RASSF1A promoter hypermethylation from peripheral blood in TCGT. We confirmed that finding in our cohort study, which represents the first report of changed RASSF1A promoter methylation in peripheral blood TGCT.
RAS 关联结构域家族蛋白 1a（RASSF1A）是一种重要的肿瘤抑制基因，在睾丸生殖细胞肿瘤（TGCT）中其启动子甲基化发生改变。RASSF1A 启动子高甲基化可能是 TGCT 肿瘤发生的早期事件。我们研究了 TGCT 患者外周血中 RASSF1A 启动子甲基化是否与睾丸癌风险相关。
在进行荟萃分析之后，我们开展了一项队列研究，纳入 32 例睾丸癌患者和 32 例健康对照。使用外周血 DNA 的亚硫酸氢盐焦磷酸测序分析 RASSF1A 和 O -甲基鸟嘌呤 - DNA -甲基转移酶（MGMT）基因的启动子甲基化情况。
荟萃分析显示，RASSF1A 启动子甲基化作为 TGCT 的危险因素，其优势比（OR）为 7.69。队列研究发现 TGCT 患者血液中 RASSF1A 启动子甲基化发生改变。在接受 BEP 化疗前，TGCT 患者的甲基化水平更高。
荟萃分析表明外周血中 RASSF1A 启动子高甲基化在 TCGT 中发挥作用。我们在队列研究中证实了这一发现，这是外周血 TGCT 中 RASSF1A 启动子甲基化改变的首次报道。
