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Identification of differentially methylated genes in the malignant transformation of ovarian endometriosis
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 m...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105232/ https://www.ncbi.nlm.nih.gov/pubmed/25298284 http://dx.doi.org/10.1186/1757-2215-7-73 |
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author | Ren, Fang Wang, Dan-Bo Li, Tong Chen, Ying-Han Li, Yan |
author_facet | Ren, Fang Wang, Dan-Bo Li, Tong Chen, Ying-Han Li, Yan |
author_sort | Ren, Fang |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4105232 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-41052322014-07-22 Identification of differentially methylated genes in the malignant transformation of ovarian endometriosis Ren, Fang Wang, Dan-Bo Li, Tong Chen, Ying-Han Li, Yan J Ovarian Res Research 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. BioMed Central 2014-07-10 /pmc/articles/PMC4105232/ /pubmed/25298284 http://dx.doi.org/10.1186/1757-2215-7-73 Text en Copyright © 2014 Ren et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Ren, Fang Wang, Dan-Bo Li, Tong Chen, Ying-Han Li, Yan Identification of differentially methylated genes in the malignant transformation of ovarian endometriosis |
title | Identification of differentially methylated genes in the malignant transformation of ovarian endometriosis |
title_full | Identification of differentially methylated genes in the malignant transformation of ovarian endometriosis |
title_fullStr | Identification of differentially methylated genes in the malignant transformation of ovarian endometriosis |
title_full_unstemmed | Identification of differentially methylated genes in the malignant transformation of ovarian endometriosis |
title_short | Identification of differentially methylated genes in the malignant transformation of ovarian endometriosis |
title_sort | identification of differentially methylated genes in the malignant transformation of ovarian endometriosis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105232/ https://www.ncbi.nlm.nih.gov/pubmed/25298284 http://dx.doi.org/10.1186/1757-2215-7-73 |
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