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Int. J. Mol. Sci. 2018, 19(6), 1559; https://doi.org/10.3390/ijms19061559

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

1
Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy
2
Unit of Pathology, Azienda Ospedaliero-Universitaria Policlinico, 41124 Modena, Italy
3
Institute of Pathology, Lausanne University Hospital, 1011 Lausanne, Switzerland
4
Aurigen, Centre de Génétique et Pathologie, 1004 Lausanne, Switzerland
*
Author to whom correspondence should be addressed.
Received: 14 April 2018 / Revised: 18 May 2018 / Accepted: 18 May 2018 / Published: 24 May 2018
(This article belongs to the Special Issue Ovarian Cancer: Pathogenesis, Diagnosis, and Treatment)
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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 (BRCA1, MGMT, and MLH1), 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 MGMT, OSMR, ESR1, and FOXL2 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. View Full-Text
Keywords: ovarian carcinoma; DNA methylation profiling; Wnt pathway; DNA damage repair system; TERT; MGMT; BRCA1; MLH1; OSMR; ESR1; FOXL2 ovarian carcinoma; DNA methylation profiling; Wnt pathway; DNA damage repair system; TERT; MGMT; BRCA1; MLH1; OSMR; ESR1; FOXL2
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Losi, L.; Fonda, S.; Saponaro, S.; Chelbi, S.T.; Lancellotti, C.; Gozzi, G.; Alberti, L.; Fabbiani, L.; Botticelli, L.; Benhattar, J. Distinct DNA Methylation Profiles in Ovarian Tumors: Opportunities for Novel Biomarkers. Int. J. Mol. Sci. 2018, 19, 1559.

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