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学科主题: 基础医学
题名:
Gene promoter methylation patterns throughout the process of cervical carcinogenesis
作者: Yang, Nan1,2; Nijhuis, Esther R.1; Volders, Haukeline H.1; Eijsink, Jasper J. H.1; Lendvai, Agnes1; Zhang, Bo2; Hollema, Harry3; Schuuring, Ed3; Wisman, G. Bea A.1; van der Zee, Ate G. J.1
关键词: Methylation ; cervical (intraepithelial) neoplasia ; DAPK ; CCNA1 ; CADM1
刊名: CELLULAR ONCOLOGY
发表日期: 2010
DOI: 10.3233/CLO-2009-0510
卷: 32, 期:1-2, 页:131-143
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology ; Cell Biology ; Pathology
研究领域[WOS]: Oncology ; Cell Biology ; Pathology
关键词[WOS]: ABERRANT DNA METHYLATION ; HUMAN-PAPILLOMAVIRUS DNA ; SQUAMOUS-CELL CARCINOMA ; UTERINE CERVIX ; CANCER ; HYPERMETHYLATION ; NEOPLASIA ; PCR ; PREVALENCE ; EXPRESSION
英文摘要:

Objectives: To determine methylation status of nine genes, previously described to be frequently methylated in cervical cancer, in squamous intraepithelial lesions (SIL).

Methods: QMSP was performed in normal cervix, low-grade ( L) SIL, high-grade (H) SIL, adenocarcinomas and squamous cell cervical cancers, and in corresponding cervical scrapings.

Results: Only CCNA1 was never methylated in normal cervices and rarely in LSILs. All other genes showed methylation in normal cervices, with CALCA, SPARC and RAR-beta(2) at high levels. Methylation frequency of 6 genes (DAPK, APC, TFPI2, SPARC, CCNA1 and CADM1) increased with severity of the underlying cervical lesion. DAPK showed the highest increase in methylation frequency between LSIL and HSIL (10% vs. 40%, p < 0.05), while CCNA1 and TFPI2 were most prominently methylated in cervical cancers compared to HSILs (25% vs. 52%, p < 0.05, 30% vs. 58%, p < 0.05). CADM1 methylation in cervical cancers was related to depth of invasion ( p < 0.05) and lymph vascular space involvement ( p < 0.01), suggesting a role in invasive potential of cervical cancers. Methylation ratios in scrapings reflected methylation status of the underlying lesions ( p < 0.05).

Conclusion: Methylation of previously reported cervical cancer specific genes frequently occurs in normal epithelium. However, frequency of methylation increases during cervical carcinogenesis, with CCNA1 and DAPK as the best markers to distinguish normal/LSIL from HSIL/cancer lesions.

语种: 英语
所属项目编号: RUG 2004-3161
项目资助者: Dutch Cancer Society (NKB)
WOS记录号: WOS:000276461800012
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50288
Appears in Collections:基础医学院_病理学系_期刊论文

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作者单位: 1.Univ Groningen, Dept Gynecol Oncol, Univ Med Ctr Groningen, NL-9700 RB Groningen, Netherlands
2.Peking Univ, Dept Pathol, Sch Basic Med Sci, Hlth Sci Ctr, Beijing 100871, Peoples R China
3.Univ Groningen, Dept Pathol, Univ Med Ctr Groningen, NL-9700 RB Groningen, Netherlands

Recommended Citation:
Yang, Nan,Nijhuis, Esther R.,Volders, Haukeline H.,et al. Gene promoter methylation patterns throughout the process of cervical carcinogenesis[J]. CELLULAR ONCOLOGY,2010,32(1-2):131-143.
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