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RASSF1A 和 APC 基因启动子甲基化异常与卵巢上皮性癌的发生。

Aberrant promoter methylation of the RASSF1A and APC genes in epithelial ovarian carcinoma development.

机构信息

Department of Biochemistry, Kidwai Memorial Institute of Oncology, Bangalore, India.

出版信息

Cell Oncol (Dordr). 2012 Dec;35(6):473-9. doi: 10.1007/s13402-012-0106-4. Epub 2012 Oct 10.

DOI:10.1007/s13402-012-0106-4
PMID:23055343
Abstract

PURPOSE

Tumor suppressor gene (TSG) silencing through promoter hypermethylation plays an important role in cancer development. The aim of this study was to assess the extent of methylation of the RASSF1A and APC TSG promoters in ovarian epithelial adenomas, low malignant potential tumours and carcinomas in order to reveal a role for epigenetic TSG silencing in the development of these ovarian malignancies.

METHOD

The promoter methylation status of the RASSF1A and APC genes was assessed in 19 benign cystadenomas, 14 low malignant potential (LMP) tumours, and 86 carcinomas using methylation specific PCR (MSP).

RESULTS

The methylation frequencies of the RASSF1A and APC gene promoters in benign cystadenomas were found to be 37 % and 16 %, respectively. The LMP tumours exhibited RASSF1A and APC gene promoter methylation frequencies of 50 % and 28 %, respectively, whereas the carcinomas exhibited methylation frequencies of 58 % and 29 %, respectively. Methylation of either the RASSF1A or the APC gene promoter was encountered in 58 % of the invasive carcinomas.

CONCLUSION

The observed aberrant methylation frequencies of the RASSF1A and APC gene promoters indicate that an accumulation of epigenetic events at these specific TSG promoters may be associated with the malignant transformation of benign cystadenomas and LMP tumours to carcinomas.

摘要

目的

肿瘤抑制基因(TSG)通过启动子超甲基化沉默在癌症发展中起着重要作用。本研究旨在评估 RASSF1A 和 APC TSG 启动子在卵巢上皮性腺瘤、低度恶性潜能肿瘤和癌中的甲基化程度,以揭示表观遗传 TSG 沉默在这些卵巢恶性肿瘤发展中的作用。

方法

采用甲基化特异性 PCR(MSP)检测 19 例良性囊腺瘤、14 例低度恶性潜能(LMP)肿瘤和 86 例癌中 RASSF1A 和 APC 基因启动子的甲基化状态。

结果

良性囊腺瘤中 RASSF1A 和 APC 基因启动子的甲基化频率分别为 37%和 16%。LMP 肿瘤中 RASSF1A 和 APC 基因启动子的甲基化频率分别为 50%和 28%,而癌中 RASSF1A 和 APC 基因启动子的甲基化频率分别为 58%和 29%。侵袭性癌中存在 RASSF1A 或 APC 基因启动子甲基化的比例为 58%。

结论

RASSF1A 和 APC 基因启动子异常甲基化频率的观察表明,这些特定 TSG 启动子的表观遗传事件积累可能与良性囊腺瘤和 LMP 肿瘤向癌的恶性转化有关。

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