Distinct DNA Methylation Profiles in Ovarian Tumors: Opportunities for Novel Biomarkers.

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State: Public
Version: Final published version
Serval ID
serval:BIB_DD6BD464A973
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Distinct DNA Methylation Profiles in Ovarian Tumors: Opportunities for Novel Biomarkers.
Journal
International journal of molecular sciences
Author(s)
Losi L., Fonda S., Saponaro S., Chelbi S.T., Lancellotti C., Gozzi G., Alberti L., Fabbiani L., Botticelli L., Benhattar J.
ISSN
1422-0067 (Electronic)
ISSN-L
1422-0067
Publication state
Published
Issued date
24/05/2018
Peer-reviewed
Oui
Volume
19
Number
6
Pages
1559
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Aberrant methylation of multiple promoter CpG islands could be related to the biology of ovarian tumors and its determination could help to improve treatment strategies. DNA methylation profiling was performed using the Methylation Ligation-dependent Macroarray (MLM), an array-based analysis. Promoter regions of 41 genes were analyzed in 102 ovarian tumors and 17 normal ovarian samples. An average of 29% of hypermethylated promoter genes was observed in normal ovarian tissues. This percentage increased slightly in serous, endometrioid, and mucinous carcinomas (32%, 34%, and 45%, respectively), but decreased in germ cell tumors (20%). Ovarian tumors had methylation profiles that were more heterogeneous than other epithelial cancers. Unsupervised hierarchical clustering identified four groups that are very close to the histological subtypes of ovarian tumors. Aberrant methylation of three genes ( <i>BRCA1</i> , <i>MGMT</i> , and <i>MLH1</i> ), playing important roles in the different DNA repair mechanisms, were dependent on the tumor subtype and represent powerful biomarkers for precision therapy. Furthermore, a promising relationship between hypermethylation of <i>MGMT</i> , <i>OSMR</i> , <i>ESR1</i> , and <i>FOXL2</i> and overall survival was observed. Our study of DNA methylation profiling indicates that the different histotypes of ovarian cancer should be treated as separate diseases both clinically and in research for the development of targeted therapies.
Keywords
Biomarkers, Tumor/metabolism, Cluster Analysis, DNA Methylation/genetics, Female, Humans, Kaplan-Meier Estimate, Ovarian Neoplasms/genetics, Promoter Regions, Genetic, BRCA1, DNA damage repair system, DNA methylation profiling, ESR1, FOXL2, MGMT, MLH1, OSMR, TERT, Wnt pathway, ovarian carcinoma
Pubmed
Web of science
Open Access
Yes
Create date
14/06/2018 17:09
Last modification date
20/08/2019 17:02
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