宫颈癌中 DAPK1、FHIT、MGMT 和 CDKN2A 基因的启动子甲基化。
Promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A genes in cervical carcinoma.
机构信息
Division of Obstetrics and Gynecology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Chuo Ward, Niigata, 951-8510, Japan,
出版信息
Int J Clin Oncol. 2014 Feb;19(1):127-32. doi: 10.1007/s10147-013-0530-0. Epub 2013 Mar 14.
BACKGROUND AND OBJECTIVES
Aberrant DNA methylation contributes to the malignant phenotype in virtually all types of human cancer. This study explored the relationship between promoter methylation and inactivation of the DAPK1, FHIT, MGMT, and CDKN2A genes in cervical cancer.
METHODS
The promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A was investigated by using a methylation-specific polymerase chain reaction in 53 specimens of cervical cancer (42 squamous cell carcinoma, 11 adenocarcinoma), 22 specimens of intraepithelial neoplasia tissues, and 24 control normal cervical tissue specimens. The correlation of promoter methylation with the clinicopathological features of cervical cancer was analyzed. The expressions of DAPK1, FHIT, MGMT, and CDKN2A were detected by measuring relative mRNA levels.
RESULTS
The promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A in cervical cancer vs. intraepithelial neoplasia vs. normal cervical tissue was 75.5 vs. 31.8 vs. 4.2 % (p < 0.0001), 66.0 vs. 59.1 vs. 25.0 % (p = 0.0033), 34.0 vs. 27.3 vs. 20.8 % (p = 0.76), and 17.0 vs. 31.8 vs. 8.3 % (p = 0.11), respectively. The methylation of the promoter region significantly decreased the expression of only DAPK1 (p = 0.03). The methylation rate of the DAPK1 gene promoter was significantly higher in cervical cancer tissues than in cervical intraepithelial neoplasia and normal cervical tissues.
CONCLUSION
Promoter methylation may therefore lead to the inactivation of the DAPK1 gene, and may be related to the progression of cervical oncogenesis.
背景与目的
异常的 DNA 甲基化几乎与所有类型的人类癌症的恶性表型有关。本研究探讨了宫颈癌中 DAPK1、FHIT、MGMT 和 CDKN2A 基因启动子甲基化与失活的关系。
方法
采用甲基化特异性聚合酶链反应检测 53 例宫颈癌（42 例鳞状细胞癌，11 例腺癌）、22 例上皮内瘤变组织和 24 例正常宫颈组织标本中 DAPK1、FHIT、MGMT 和 CDKN2A 的启动子甲基化情况。分析启动子甲基化与宫颈癌临床病理特征的相关性。通过测量相对 mRNA 水平检测 DAPK1、FHIT、MGMT 和 CDKN2A 的表达。
结果
宫颈癌、上皮内瘤变和正常宫颈组织中 DAPK1、FHIT、MGMT 和 CDKN2A 的启动子甲基化率分别为 75.5%、31.8%和 4.2%（p<0.0001）、66.0%、59.1%和 25.0%（p=0.0033）、34.0%、27.3%和 20.8%（p=0.76）和 17.0%、31.8%和 8.3%（p=0.11）。只有 DAPK1 的启动子区域的甲基化显著降低了其表达（p=0.03）。DAPK1 基因启动子的甲基化率在宫颈癌组织中明显高于宫颈上皮内瘤变和正常宫颈组织。
结论
启动子甲基化可能导致 DAPK1 基因失活，并可能与宫颈癌发生的进展有关。
Zotero 插件