Lattario F, Furtado Y L, Fonseca R, Silveira F A, do Val I C, Almeida G, Carvalho M G C
Gene Expression Control Laboratory, Carlos Chagas Filho Institute of Biophysics and Institute of Gynecology, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Int J Gynecol Cancer. 2008 Jul-Aug;18(4):785-9. doi: 10.1111/j.1525-1438.2007.01060.x. Epub 2007 Sep 14.
This study was conducted to investigate the presence of Epstein-Barr virus (EBV) and human papillomavirus (HPV) and the promoter methylation status of the death-associated protein kinase (DAPK) gene in high-grade intraepithelial lesions. Viral infection was analyzed using polymerase chain reaction (PCR), and promoter methylation status was evaluated using chemical modification by sodium bisulfite followed by PCR. A total of 24 samples were studied. HPV was detected in 16.6%, EBV in 16.6%, and HPV/EBV coinfection in 16.6%. No virus infection was detected in 50% of the samples studied. DAPK promoter methylation was observed in 29.2% of the analyzed samples. There was no significant correlation between DAPK methylation and viral infection. DAPK methylation was detected in 28% of HPV-positive lesions, in 28% of HPV- and EBV-positive lesions, and in 44% (3/7) of the samples without viral infection. There was no observed methylation in samples with isolated EBV infection. In DAPK unmethylated samples, HPV infection was found in 12%, EBV infection in 23%, HPV/EBV coinfection in 12%, and an absence of HPV and EBV infection in 53%. The promoter methylation of the DAPK gene is an important event during carcinogenesis and may have potential clinical application as a marker for the progression and prognosis of cancer.
本研究旨在调查高级别上皮内瘤变中爱泼斯坦-巴尔病毒(EBV)和人乳头瘤病毒(HPV)的存在情况以及死亡相关蛋白激酶(DAPK)基因的启动子甲基化状态。采用聚合酶链反应(PCR)分析病毒感染情况,并通过亚硫酸氢钠化学修饰后进行PCR评估启动子甲基化状态。共研究了24个样本。HPV检测阳性率为16.6%,EBV为16.6%,HPV/EBV合并感染为16.6%。50%的研究样本未检测到病毒感染。在29.2%的分析样本中观察到DAPK启动子甲基化。DAPK甲基化与病毒感染之间无显著相关性。在28%的HPV阳性病变、28%的HPV和EBV阳性病变以及44%(3/7)无病毒感染的样本中检测到DAPK甲基化。在孤立EBV感染的样本中未观察到甲基化。在DAPK未甲基化的样本中,HPV感染率为12%,EBV感染率为23%,HPV/EBV合并感染率为12%,53%未感染HPV和EBV。DAPK基因的启动子甲基化是致癌过程中的一个重要事件,可能作为癌症进展和预后的标志物具有潜在的临床应用价值。