CpG methylation of HPV 16 LCR at E2 binding site proximal to P97 is associated with cervical cancer in presence of intact E2
CpG methylation of HPV 16 LCR at E2 binding site proximal to P97 is associated with cervical cancer in presence of intact E2
复制标题
DOI：
10.1016/j.virol.2006.06.018
复制
发表时间：
2006-10-25
期刊：
影响因子：
3.7
通讯作者：
Sengupta, Sharmila
中科院分区：
文献类型：
--
作者：
Bhattacharjee, Bornali;Sengupta, Sharmila
人乳头瘤病毒16型(HPV-16)E2蛋白负性调节E6和E7基因的转录。本研究旨在验证HPV16长控制区(LCR)甲基化在宫颈癌(CaCx)病例中的表达高于含有完整E2基因的细胞学正常对照的假说。用HpaII/MspI限制性内切酶分析P97启动子附近的E2结合位点(E213S-I)的甲基化，用McrBC酶切法检测57例CaCx和15例正常对照的LCR-E6(7289-540)。病例组E2BS-I甲基化发生率(56.14%)显著高于对照组(20%)[经年龄调整(95%可信区间)：4.53(1.05-19.43)p=0.042]。在LCR-E6甲基化状态方面，病例组(54.39%)和对照组(40%)之间的差异无统计学意义[ORGE调整(95%CI)：1.77(0.5-6.3)；p=0.38]。对随机选择的13个甲基化的恶性肿瘤样本进行测序，发现分别在CPGS 7579、7535、7683和7862处没有或罕见地存在甲基化。在P97启动子附近的E2结合部位，发现CPGS上的甲基化程度更高。这些结果表明，在完整的E2存在的情况下，参与了E2结合部位的甲基化，导致了CaCx中E2抑制活性的丧失。(C)2006 Elsevier Inc.保留所有权利。
Human papilloinavirus type 16 (HPV-16) E2 protein negatively regulates transcription of the E6 and E7 genes. This study was done to test the hypothesis that methylation of the HPV 16 long control region (LCR) is overrepresented among cervical cancer (CaCx) cases compared to cytologically normal controls harboring intact E2 gene. Methylation of the E2 binding site (E213S-I), proximal to the P97 promoter, was assessed by HpaII/MspI restriction digestion while McrBC digestion was used to assess LCR-E6 (7289-540) for 57 CaCx samples and 15 normal controls. E2BS-I methylation was found to be significantly higher (56.14%) in cases compared to (20%) controls [ORage-adjusted (95% CI): 4.53 (1.05-19.43) p=0.042]. The difference between cases (54.39%) and controls (40%) with respect to LCR-E6 methylation status [ORage-adjusted (95% CI): 1.77(0.5-6.3); p=0.38] was not significant. Sequencing of a randomly selected set of 13 methylated malignant samples revealed absence or rare presence, of methylation at CpGs 7579, 7535, 7683 and 7862 respectively. Methylation was found to be more at CpGs within E2 binding sites proximal to the P97 promoter. These results indicate the involvement of E2 binding site methylation in presence of intact E2, leading to loss of E2 repressor activity in CaCx. (c) 2006 Elsevier Inc. All rights reserved.