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学科主题: 临床医学
题名:
Hypermethylation of RAS effector related genes and DNA methyltransferase 1 expression in endometrial carcinogenesis
作者: Liao, Xiaoyun1,2; Siu, Michelle Kwan-Yee1; Chan, Kelvin Yuen-Kwong1; Wong, Esther Shuk-Ying1; Ngan, Hextan Yuen-Sheung3; Chan, Queeny Kwan-Yi1; Li, Albert Siu-Ming1; Khoo, Ui-Soon1; Cheung, Annie Nga-Yin1
关键词: DNA hypermethylation ; endometrial cancer ; DNMT1 ; RASSF1A ; RASSF2A ; hDAB2IP ; BLU
刊名: INTERNATIONAL JOURNAL OF CANCER
发表日期: 2008-07-15
DOI: 10.1002/ijc.23494
卷: 123, 期:2, 页:296-302
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: ABERRANT PROMOTER METHYLATION ; TUMOR-SUPPRESSOR GENE ; PROTEIN HDAB2IP GENE ; FREQUENT EPIGENETIC INACTIVATION ; GLUTATHIONE-S-TRANSFERASE ; MULTIPLE CPG ISLANDS ; HUMAN CANCER-CELLS ; K-RAS ; DNMT1 PROTEIN ; PROSTATE-CANCER
英文摘要:

Epigenetic aberration is known to be important in human carcinogenesis. Promoter methylation status of RAS effector related genes, RASSF1A, RASSF2A, hDAB2IP (m2a and m2b regions) and BLU, was evaluated in 76 endometrial carcinomas and their non-neoplastic endometrial tissue by methylation specific PCR. Hypermethylation of at least one of the 5 genes was detected in 73.7% of carcinomas. There were significant correlations between methylation of hDAB2IP and RASSF1A, RASSF2A (p = 0.042, p = 0.012, respectively). Significantly, more frequent RASSF1A hypermethylation was found in Type I endometrioid carcinomas than Type II carcinomas (p = 0.049). Among endometrioid cancers, significant association between RASSF1A hypermethylation and advanced stage, as well as between methylation of hDAB2IP at m2a region with deep myometrial invasion (p < 0.05) was observed. mRNA expression of RASSF1A, RASSF2A and BLU in endometrial cancer cell lines significantly increased after treatment with the demethylating agent 5-Aza-2′-deoxycytidine supporting the repressive effect of hypermethylation on their transcription. Immunohistochemical study of DNMT1 on eight normal endometrium, 16 hyperplastic endometrium without atypia, 40 atypical complex hyperplasia and 79 endometrial carcinomas showed progressive increase in DNMT1 immunoreactivity from normal endometrium to endometrial hyperplasia and endometrioid carcinomas (p = 0.001). Among carcinomas, distinctly higher DNMT1 expression was observed in Type I endometrioid carcinomas (p < 0.001). DNMT1 immunoreactivity correlated with RASSF1A and RASSF2A methylation (p < 0.05). The data suggested that hypermethylation of RAS related genes, particularly RASSF1A, was involved in endometrial carcinogenesis with possible divergent patterns in different histological types. DNMT1 protein overexpression might contribute to such aberrant DNA hypermethylation of specific tumor suppressor genes in endometrial cancers. (C) 2008 Wiley-Liss, Inc.

语种: 英语
WOS记录号: WOS:000256760300008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59898
Appears in Collections:北京大学第二临床医学院_病理科_期刊论文

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作者单位: 1.Univ Hong Kong, Queen Mary Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China
2.Peking Univ, Peoples Hosp, Dept Pathol, Beijing 100871, Peoples R China
3.Univ Hong Kong, Dept Obstet & Gynaecol, Hong Kong, Peoples R China

Recommended Citation:
Liao, Xiaoyun,Siu, Michelle Kwan-Yee,Chan, Kelvin Yuen-Kwong,et al. Hypermethylation of RAS effector related genes and DNA methyltransferase 1 expression in endometrial carcinogenesis[J]. INTERNATIONAL JOURNAL OF CANCER,2008,123(2):296-302.
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