Identification of differentially methylated genes in the malignant transformation of ovarian endometriosis

Journal of Ovarian Research

Yan Li¹  Ying-Han Chen¹  Tong Li¹  Dan-Bo Wang¹  Fang Ren¹ 

[1] Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang 110004, China

关键词: RASSF2;    Methylation;    Malignant transformation;    Endometriosis;    Ovarian carcinoma;   

Others  :  1151825
DOI  :  10.1186/1757-2215-7-73

 received in 2014-04-25, accepted in 2014-07-07,  发布年份 2014

【 摘 要 】

Background

Key roles for epigenetic mechanisms in tumorigenesis are well accepted, while the relationship between gene methylation and malignant transformation of ovarian endometriosis (EMS) was seldom reported. In this study, we aimed to screen for aberrantly methylated genes associated with the malignant transformation of ovarian EMS and to preliminarily verify the reliability of screened results by detecting the methylation status and protein expression of the candidate gene in a larger scale of formaldehyde-fixed and paraffin-embedded (FFPE) samples.

Methods

Methylated CpG island amplification coupled with representational difference analysis (MCA-RDA) was performed on 3 couples of endometriosis-associated ovarian carcinoma (EAOC) fresh samples to identify differentially methylated candidate genes related to malignant transformation of ovarian EMS; Methylation-specific PCR (MSP) and immunohistochemistry were performed in 30 EAOC samples to detected the methylation status and protein expression of RASSF2 gene to verify the reliability of MCA-RDA results.

Results

Nine differentially methylated genes were obtained by MCA-RDA as candidate genes for malignant transformation of EMS; Methylation frequency of RASSF2 in the neoplastic tissues of EAOC group was higher than that in the ectopic endometria (p < 0.05). While protein expression of RASSF2 in the neoplastic tissues was lower than that in the ectopic endometria of the EAOC group (p < 0.05) Absence of protein expression of RASSF2 was significantly correlated with the promoter methylation of the gene (p < 0.05).

Conclusions

RASSF2, RUNX3, GSTZ1, CYP2A, GBGT1, NDUFS1, SPOCK2, ADAM22, and TRIM36 were candidate genes for malignant transformation of ovarian EMS and epigenetic inactivation of RASSF2 by promoter hypermethylation is an early event in malignant transformation of ovarian EMS. The screen results were reliable and worthy of further study.

【 授权许可】

   
2014 Ren et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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