The early pregnancy placenta foreshadows DNA methylation alterations of solid tumors
The placenta relies on phenotypes that are characteristic of cancer to successfully implant the embryo in the uterus during early pregnancy. Notably, it has to invade its host tissues, promote angiogenesis—while surviving hypoxia—, and escape the immune system. Similarities in DNA methylation patter...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-09-01
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| Series: | Epigenetics |
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| Online Access: | http://dx.doi.org/10.1080/15592294.2017.1342912 |
| _version_ | 1827811609656950784 |
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| author | Akpéli V. Nordor Djamel Nehar-Belaid Sophie Richon David Klatzmann Dominique Bellet Virginie Dangles-Marie Thierry Fournier Martin J. Aryee |
| author_facet | Akpéli V. Nordor Djamel Nehar-Belaid Sophie Richon David Klatzmann Dominique Bellet Virginie Dangles-Marie Thierry Fournier Martin J. Aryee |
| author_sort | Akpéli V. Nordor |
| collection | DOAJ |
| description | The placenta relies on phenotypes that are characteristic of cancer to successfully implant the embryo in the uterus during early pregnancy. Notably, it has to invade its host tissues, promote angiogenesis—while surviving hypoxia—, and escape the immune system. Similarities in DNA methylation patterns between the placenta and cancers suggest that common epigenetic mechanisms may be involved in regulating these behaviors. We show here that megabase-scale patterns of hypomethylation distinguish first from third trimester chorionic villi in the placenta, and that these patterns mirror those that distinguish many tumors from corresponding normal tissues. We confirmed these findings in villous cytotrophoblasts isolated from the placenta and identified a time window at the end of the first trimester, when these cells come into contact with maternal blood, as the likely time period for the methylome alterations. Furthermore, the large genomic regions affected by these patterns of hypomethylation encompass genes involved in pathways related to epithelial-mesenchymal transition, immune response, and inflammation. Analyses of expression profiles corresponding to genes in these hypomethylated regions in colon adenocarcinoma tumors point to networks of differentially expressed genes previously implicated in carcinogenesis and placentogenesis, where nuclear factor kappa B is a key hub. Taken together, our results suggest the existence of epigenetic switches involving large-scale changes of methylation in the placenta during pregnancy and in tumors during neoplastic transformation. The characterization of such epigenetic switches might lead to the identification of biomarkers and drug targets in oncology as well as in obstetrics and gynecology. |
| first_indexed | 2024-03-11T23:07:04Z |
| format | Article |
| id | doaj.art-0352197b59a447b78d30ca7d40d9ee16 |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:07:04Z |
| publishDate | 2017-09-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-0352197b59a447b78d30ca7d40d9ee162023-09-21T12:43:13ZengTaylor & Francis GroupEpigenetics1559-22941559-23082017-09-0112979380310.1080/15592294.2017.13429121342912The early pregnancy placenta foreshadows DNA methylation alterations of solid tumorsAkpéli V. Nordor0Djamel Nehar-Belaid1Sophie Richon2David Klatzmann3Dominique Bellet4Virginie Dangles-Marie5Thierry Fournier6Martin J. Aryee7Institut Curie, PSL Research UniversitySorbonne Universités, UPMC University of ParisInstitut Curie, PSL Research University, CNRSSorbonne Universités, UPMC University of ParisChimie ParisTech, PSL Research University, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS)Institut Curie, PSL Research UniversityINSERM, U1139Massachusetts General Hospital and Harvard Medical SchoolThe placenta relies on phenotypes that are characteristic of cancer to successfully implant the embryo in the uterus during early pregnancy. Notably, it has to invade its host tissues, promote angiogenesis—while surviving hypoxia—, and escape the immune system. Similarities in DNA methylation patterns between the placenta and cancers suggest that common epigenetic mechanisms may be involved in regulating these behaviors. We show here that megabase-scale patterns of hypomethylation distinguish first from third trimester chorionic villi in the placenta, and that these patterns mirror those that distinguish many tumors from corresponding normal tissues. We confirmed these findings in villous cytotrophoblasts isolated from the placenta and identified a time window at the end of the first trimester, when these cells come into contact with maternal blood, as the likely time period for the methylome alterations. Furthermore, the large genomic regions affected by these patterns of hypomethylation encompass genes involved in pathways related to epithelial-mesenchymal transition, immune response, and inflammation. Analyses of expression profiles corresponding to genes in these hypomethylated regions in colon adenocarcinoma tumors point to networks of differentially expressed genes previously implicated in carcinogenesis and placentogenesis, where nuclear factor kappa B is a key hub. Taken together, our results suggest the existence of epigenetic switches involving large-scale changes of methylation in the placenta during pregnancy and in tumors during neoplastic transformation. The characterization of such epigenetic switches might lead to the identification of biomarkers and drug targets in oncology as well as in obstetrics and gynecology.http://dx.doi.org/10.1080/15592294.2017.1342912cancerdna methylationepigenomicsepigeneticshypomethylationplacentapregnancy |
| spellingShingle | Akpéli V. Nordor Djamel Nehar-Belaid Sophie Richon David Klatzmann Dominique Bellet Virginie Dangles-Marie Thierry Fournier Martin J. Aryee The early pregnancy placenta foreshadows DNA methylation alterations of solid tumors Epigenetics cancer dna methylation epigenomics epigenetics hypomethylation placenta pregnancy |
| title | The early pregnancy placenta foreshadows DNA methylation alterations of solid tumors |
| title_full | The early pregnancy placenta foreshadows DNA methylation alterations of solid tumors |
| title_fullStr | The early pregnancy placenta foreshadows DNA methylation alterations of solid tumors |
| title_full_unstemmed | The early pregnancy placenta foreshadows DNA methylation alterations of solid tumors |
| title_short | The early pregnancy placenta foreshadows DNA methylation alterations of solid tumors |
| title_sort | early pregnancy placenta foreshadows dna methylation alterations of solid tumors |
| topic | cancer dna methylation epigenomics epigenetics hypomethylation placenta pregnancy |
| url | http://dx.doi.org/10.1080/15592294.2017.1342912 |
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