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学科主题: 临床医学
题名:
Differential DNA methylation profiles in gynecological cancers and correlation with clinico-pathological data
作者: Yang, Hui-Juan; Liu, Vincent W. S.; Wang, Yue; Tsang, Percy C. K.; Ngan, Hextan Y. S.
刊名: BMC CANCER
发表日期: 2006-08-23
DOI: 10.1186/1471-2407-6-212
卷: 6
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]: MICROSATELLITE INSTABILITY PHENOTYPE ; TUMOR-SUPPRESSOR GENES ; CPG-ISLAND METHYLATION ; BRCA1 PROMOTER REGION ; ENDOMETRIAL CARCINOMAS ; SPORADIC BREAST ; CERVICAL-CANCER ; MULTIPLE GENES ; PROTEIN-KINASE ; OVARIAN-TUMORS
英文摘要:

Background: Epigenetic gene silencing is one of the major causes of carcinogenesis. Its widespread occurrence in cancer genome could inactivate many cellular pathways including DNA repair, cell cycle control, apoptosis, cell adherence, and detoxification. The abnormal promoter methylation might be a potential molecular marker for cancer management.

Methods: For rapid identification of potential targets for aberrant methylation in gynecological cancers, methylation status of the CpG islands of 34 genes was determined using pooled DNA approach and methylation-specific PCR. Pooled DNA mixture from each cancer type (50 cervical cancers, 50 endometrial cancers and 50 ovarian cancers) was made to form three test samples. The corresponding normal DNA from the patients of each cancer type was also pooled to form the other three control samples. Methylated alleles detected in tumors, but not in normal controls, were indicative of aberrant methylation in tumors. Having identified potential markers, frequencies of methylation were further analyzed in individual samples. Markers identified are used to correlate with clinico-pathological data of tumors using chi(2) or Fisher′s exact test.

Results: APC and p16 were hypermethylated across the three cancers. MINT31 and PTEN were hypermethylated in cervical and ovarian cancers. Specific methylation was found in cervical cancer (including CDH1, DAPK, MGMT and MINT2), endometrial cancer (CASP8, CDH13, hMLH1 and p73), and ovarian cancer (BRCA1, p14, p15, RIZ1 and TMS1). The frequencies of occurrence of hypermethylation in 4 candidate genes in individual samples of each cancer type (DAPK, MGMT, p16 and PTEN in 127 cervical cancers; APC, CDH13, hMLH1 and p16 in 60 endometrial cancers; and BRCA1, p14, p16 and PTEN in 49 ovarian cancers) were examined for further confirmation. Incidence varied among different genes and in different cancer types ranging from the lowest 8.2% (PTEN in ovarian cancer) to the highest 56.7% (DAPK in cervical cancer). Aberrant methylation for some genes (BRCA1, DAPK, hMLH1, MGMT, p14, p16, and PTEN) was also associated with clinico-pathological data.

Conclusion: Thus, differential methylation profiles occur in the three types of gynecologic cancer. Detection of methylation for critical loci is potentially useful as epigenetic markers in tumor classification. More studies using a much larger sample size are needed to define the potential role of DNA methylation as marker for cancer management.

语种: 英语
WOS记录号: WOS:000240420200001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55772
Appears in Collections:北京大学第二临床医学院_期刊论文

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作者单位: 1.Univ Hong Kong, Dept Obstet & Gynecol, Hong Kong, Hong Kong, Peoples R China
2.Fudan Univ, Canc Hosp, Dept Gynecol Oncol, Shanghai 200433, Peoples R China
3.Peking Univ, Peoples Hosp, Dept Obstet & Gynecol, Beijing, Peoples R China

Recommended Citation:
Yang, Hui-Juan,Liu, Vincent W. S.,Wang, Yue,et al. Differential DNA methylation profiles in gynecological cancers and correlation with clinico-pathological data[J]. BMC CANCER,2006,6.
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