Aberrant DNA methylation in cervical carcinogenesis  

作　　者：Hui-Juan Yang 

机构地区：[1]Department of Gynecologic Oncology,Fudan University Shanghai Cancer Center

出　　处：《Chinese Journal of Cancer》2013年第1期42-48,共7页

摘　　要：Persistent infection wit h high-risk types of human papillomavirus(HPV) is known to cause cervical cancer;however,additional genetic and epigenetic alterations are required for progression from precancerous disease to invasive cancer.DNA methylation is an early and frequent molecular alteration in cervical carcinogenesis.In this review,we summarize DNA methylation within the HPV genome and human genome and identify its clinical implications.Methylation of the HPV long control region(LCR) and L1 gene is common during cervical carcinogenesis and increases with the severity of the cervical neoplasm.The L1 gene of HPV16 and HPV18 is consistently hypermethylated in invasive cervical cancers and can potentially be used as a clinical marker of cancer progression.Moreover,promoters of tumor suppressor genes(TSGs) involved in many cellular pathways are methylated in cervical precursors and invasive cancers.Some are associated with squamous cell carcinomas,and others are associated with adenocarcinomas.Identification of methylated TSGs in Pap smear could be an adjuvant test in cervical cancer screening for triage of women with high-risk HPV,atypical squamous cells of undetermined significance,or low grade squamous intraepithelial lesion(LSIL).However,consistent panels must be validated for this approach to be translated to the clinic.Furthermore,reversion of methylated TSGs using demethylating drugs may be an alternative anticancer treatment,but demethylating drugs without toxic carcinogenic and mutagenic properties must be identified and validated.Persistent infection with high-risk types cancer; however, additional genetic and of human papillomavirus（HPV） is known to cause cervical epigenetic alterations are required for progression from precancerous disease to invasive cancer. DNA methylation is an early and frequent molecular alteration in cervical carcinogenesis. In this review, we summarize DNA methylation within the HPV genome and human genome and identify its clinical implications. Methylation of the HPV long control region （LCR） and L1 gene is common during cervical carcinogenesis and increases with the severity of the cervical neoplasm. The L1 gene of HPV16 and HPV18 is consistently hypermethylated in invasive cervical cancers and can potentially be used as a clinical marker of cancer progression. Moreover, promoters of tumor suppressor genes （TSGs） involved in many cellular pathways are methylated in cervical precursors and invasive cancers. Some are associated with squamous cell carcinomas, and others are associated with adenocarcinomas. Identification of methylated TSGs in Pap smear could be an adjuvant test in cervical cancer screening for triage of women with high-risk HPV, atypical squamous cells of undetermined significance, or low grade squamous intraepithelial lesion （LSIL）. However, consistent panels must be validated for this approach to be translated to the clinic. Furthermore, reversion of methylated TSGs using demethylating drugs may be an alternative anticancer treatment, but demethylating drugs without toxic carcinogenic and mutagenic properties must be identified and validated.

关 键 词：DNA甲基化 子宫颈癌 人类基因组 HPV16 乳头状瘤病毒 异常 抑癌基因 肿瘤抑制基因 

分 类 号：R737.33[医药卫生—肿瘤]