Detection of the Placental Epigenetic Signature of the Maspin Gene in Maternal Plasma
The discovery of fetal DNA in the plasma of pregnant women has opened up new approaches for noninvasive prenatal diagnosis and monitoring. Up to now, the lack of a fetal DNA marker that can be universally detected in maternal plasma has limited the clinical application of this technology. We hypothe...
Gespeichert in:
| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2005-10, Vol.102 (41), p.14753-14758 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 14758 |
|---|---|
| container_issue | 41 |
| container_start_page | 14753 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 102 |
| creator | Stephen S. C. Chim Yu K. Tong Rossa W. K. Chiu Lau, Tze K. Leung, Tse N. Lisa Y. S. Chan Cees B. M. Oudejans Ding, Chunming Y. M. Dennis Lo |
| description | The discovery of fetal DNA in the plasma of pregnant women has opened up new approaches for noninvasive prenatal diagnosis and monitoring. Up to now, the lack of a fetal DNA marker that can be universally detected in maternal plasma has limited the clinical application of this technology. We hypothesized that epigenetic differences between the placenta and maternal blood cells could be used for developing such a marker. By using bisulfite DNA sequencing, the methylation status of the maspin gene promoter in placental tissues and paired maternal blood cells from pregnant women was analyzed. The maspin gene promoter was found to be hypomethylated in placental tissues and densely methylated in maternal blood cells. Genotyping of a single nucleotide polymorphism within the unmethylated maspin sequences in maternal plasma demonstrated that these sequences were derived from the fetus. By using real-time quantitative methylation-specific PCR, unmethylated maspin sequences were detected in maternal plasma in all three trimesters of pregnancy and were cleared within 24 h after delivery. The maternal plasma concentration of unmethylated maspin sequences was elevated by a median of 5.7 times in preeclamptic pregnancies compared with nonpreeclamptic pregnancies. Hypomethylated maspin DNA is the first universal marker for fetal DNA in maternal plasma, thus allowing the measurement of fetal DNA concentrations in pregnancy-associated disorders, irrespective of fetal gender and genetic polymorphisms. Differential DNA methylation between the placenta and maternal blood cells may be exploited to develop further markers for noninvasive prenatal assessment. |
| doi_str_mv | 10.1073/pnas.0503335102 |
| format | Article |
| fullrecord | <record><control><sourceid>jstor_pnas_</sourceid><recordid>TN_cdi_pnas_primary_102_41_14753</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>4143389</jstor_id><sourcerecordid>4143389</sourcerecordid><originalsourceid>FETCH-LOGICAL-c529t-a22a43daf025d0baedf164c90ff82ac333c526a99ff9e87f7641a74fd84c3d983</originalsourceid><addsrcrecordid>eNqF0Utv1DAQAGALgehSOHNBKOKAxCHt-JHYviChUgpSK5CgZ2vq2Fuvsk6IHQT_Hke7dIFLTz7MN-N5EPKcwgkFyU_HiOkEGuCcNxTYA7KioGndCg0PyQqAyVoJJo7Ik5Q2AKAbBY_JEW0ZcK30ily_d9nZHIZYDb7Kt6760qN1MWNfnY9h7aLLwVZfwzpinif3R11hGkOsLkq8Ku8VZjfFklOy0xafkkce--Se7d9jcv3h_NvZx_ry88Wns3eXtW2YzjUyhoJ36IE1Hdyg6zxthdXgvWJoy1DFtai199op6WUrKErhOyUs77Tix-Ttru4432xdt_Q9YW_GKWxx-mUGDObfSAy3Zj38MJQ1vBGyFHi9LzAN32eXstmGZF3fY3TDnEyrWkVl2e99kAETVCla4Kv_4GaYl9UshgpQslnQ6Q7ZaUhpcv6uZQpmOaxZDmsOhy0ZL_-e9OD3lyyg2oMl81COGUENFbLhhby5hxg_9312P3OxL3Z2k_Iw3WFBBeflt9_Vm8D8</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>201408751</pqid></control><display><type>article</type><title>Detection of the Placental Epigenetic Signature of the Maspin Gene in Maternal Plasma</title><source>Jstor Complete Legacy</source><source>MEDLINE</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Stephen S. C. Chim ; Yu K. Tong ; Rossa W. K. Chiu ; Lau, Tze K. ; Leung, Tse N. ; Lisa Y. S. Chan ; Cees B. M. Oudejans ; Ding, Chunming ; Y. M. Dennis Lo</creator><creatorcontrib>Stephen S. C. Chim ; Yu K. Tong ; Rossa W. K. Chiu ; Lau, Tze K. ; Leung, Tse N. ; Lisa Y. S. Chan ; Cees B. M. Oudejans ; Ding, Chunming ; Y. M. Dennis Lo</creatorcontrib><description>The discovery of fetal DNA in the plasma of pregnant women has opened up new approaches for noninvasive prenatal diagnosis and monitoring. Up to now, the lack of a fetal DNA marker that can be universally detected in maternal plasma has limited the clinical application of this technology. We hypothesized that epigenetic differences between the placenta and maternal blood cells could be used for developing such a marker. By using bisulfite DNA sequencing, the methylation status of the maspin gene promoter in placental tissues and paired maternal blood cells from pregnant women was analyzed. The maspin gene promoter was found to be hypomethylated in placental tissues and densely methylated in maternal blood cells. Genotyping of a single nucleotide polymorphism within the unmethylated maspin sequences in maternal plasma demonstrated that these sequences were derived from the fetus. By using real-time quantitative methylation-specific PCR, unmethylated maspin sequences were detected in maternal plasma in all three trimesters of pregnancy and were cleared within 24 h after delivery. The maternal plasma concentration of unmethylated maspin sequences was elevated by a median of 5.7 times in preeclamptic pregnancies compared with nonpreeclamptic pregnancies. Hypomethylated maspin DNA is the first universal marker for fetal DNA in maternal plasma, thus allowing the measurement of fetal DNA concentrations in pregnancy-associated disorders, irrespective of fetal gender and genetic polymorphisms. Differential DNA methylation between the placenta and maternal blood cells may be exploited to develop further markers for noninvasive prenatal assessment.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0503335102</identifier><identifier>PMID: 16203989</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Adult ; Biological Sciences ; Blood cells ; Blood plasma ; Cells ; CpG Islands - genetics ; Deoxyribonucleic acid ; DNA ; DNA - blood ; DNA - metabolism ; DNA Methylation ; Epigenetics ; Female ; Fetus ; Genes, Tumor Suppressor ; Genetic Markers - genetics ; Genetic Testing - methods ; Genetics ; Genotype ; Genotypes ; Humans ; Methylation ; Placenta ; Placenta - metabolism ; Plasma ; Polymerase chain reaction ; Polymorphism, Single Nucleotide ; Pregnancy ; Prenatal Diagnosis ; Promoter Regions, Genetic - genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; Serpins - blood ; Serpins - genetics</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2005-10, Vol.102 (41), p.14753-14758</ispartof><rights>Copyright 2005 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Oct 11, 2005</rights><rights>Copyright © 2005, The National Academy of Sciences 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c529t-a22a43daf025d0baedf164c90ff82ac333c526a99ff9e87f7641a74fd84c3d983</citedby><cites>FETCH-LOGICAL-c529t-a22a43daf025d0baedf164c90ff82ac333c526a99ff9e87f7641a74fd84c3d983</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/102/41.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/4143389$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/4143389$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16203989$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stephen S. C. Chim</creatorcontrib><creatorcontrib>Yu K. Tong</creatorcontrib><creatorcontrib>Rossa W. K. Chiu</creatorcontrib><creatorcontrib>Lau, Tze K.</creatorcontrib><creatorcontrib>Leung, Tse N.</creatorcontrib><creatorcontrib>Lisa Y. S. Chan</creatorcontrib><creatorcontrib>Cees B. M. Oudejans</creatorcontrib><creatorcontrib>Ding, Chunming</creatorcontrib><creatorcontrib>Y. M. Dennis Lo</creatorcontrib><title>Detection of the Placental Epigenetic Signature of the Maspin Gene in Maternal Plasma</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The discovery of fetal DNA in the plasma of pregnant women has opened up new approaches for noninvasive prenatal diagnosis and monitoring. Up to now, the lack of a fetal DNA marker that can be universally detected in maternal plasma has limited the clinical application of this technology. We hypothesized that epigenetic differences between the placenta and maternal blood cells could be used for developing such a marker. By using bisulfite DNA sequencing, the methylation status of the maspin gene promoter in placental tissues and paired maternal blood cells from pregnant women was analyzed. The maspin gene promoter was found to be hypomethylated in placental tissues and densely methylated in maternal blood cells. Genotyping of a single nucleotide polymorphism within the unmethylated maspin sequences in maternal plasma demonstrated that these sequences were derived from the fetus. By using real-time quantitative methylation-specific PCR, unmethylated maspin sequences were detected in maternal plasma in all three trimesters of pregnancy and were cleared within 24 h after delivery. The maternal plasma concentration of unmethylated maspin sequences was elevated by a median of 5.7 times in preeclamptic pregnancies compared with nonpreeclamptic pregnancies. Hypomethylated maspin DNA is the first universal marker for fetal DNA in maternal plasma, thus allowing the measurement of fetal DNA concentrations in pregnancy-associated disorders, irrespective of fetal gender and genetic polymorphisms. Differential DNA methylation between the placenta and maternal blood cells may be exploited to develop further markers for noninvasive prenatal assessment.</description><subject>Adult</subject><subject>Biological Sciences</subject><subject>Blood cells</subject><subject>Blood plasma</subject><subject>Cells</subject><subject>CpG Islands - genetics</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA - blood</subject><subject>DNA - metabolism</subject><subject>DNA Methylation</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Fetus</subject><subject>Genes, Tumor Suppressor</subject><subject>Genetic Markers - genetics</subject><subject>Genetic Testing - methods</subject><subject>Genetics</subject><subject>Genotype</subject><subject>Genotypes</subject><subject>Humans</subject><subject>Methylation</subject><subject>Placenta</subject><subject>Placenta - metabolism</subject><subject>Plasma</subject><subject>Polymerase chain reaction</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Pregnancy</subject><subject>Prenatal Diagnosis</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Sequence Analysis, DNA</subject><subject>Serpins - blood</subject><subject>Serpins - genetics</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0Utv1DAQAGALgehSOHNBKOKAxCHt-JHYviChUgpSK5CgZ2vq2Fuvsk6IHQT_Hke7dIFLTz7MN-N5EPKcwgkFyU_HiOkEGuCcNxTYA7KioGndCg0PyQqAyVoJJo7Ik5Q2AKAbBY_JEW0ZcK30ily_d9nZHIZYDb7Kt6760qN1MWNfnY9h7aLLwVZfwzpinif3R11hGkOsLkq8Ku8VZjfFklOy0xafkkce--Se7d9jcv3h_NvZx_ry88Wns3eXtW2YzjUyhoJ36IE1Hdyg6zxthdXgvWJoy1DFtai199op6WUrKErhOyUs77Tix-Ttru4432xdt_Q9YW_GKWxx-mUGDObfSAy3Zj38MJQ1vBGyFHi9LzAN32eXstmGZF3fY3TDnEyrWkVl2e99kAETVCla4Kv_4GaYl9UshgpQslnQ6Q7ZaUhpcv6uZQpmOaxZDmsOhy0ZL_-e9OD3lyyg2oMl81COGUENFbLhhby5hxg_9312P3OxL3Z2k_Iw3WFBBeflt9_Vm8D8</recordid><startdate>20051011</startdate><enddate>20051011</enddate><creator>Stephen S. C. Chim</creator><creator>Yu K. Tong</creator><creator>Rossa W. K. Chiu</creator><creator>Lau, Tze K.</creator><creator>Leung, Tse N.</creator><creator>Lisa Y. S. Chan</creator><creator>Cees B. M. Oudejans</creator><creator>Ding, Chunming</creator><creator>Y. M. Dennis Lo</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20051011</creationdate><title>Detection of the Placental Epigenetic Signature of the Maspin Gene in Maternal Plasma</title><author>Stephen S. C. Chim ; Yu K. Tong ; Rossa W. K. Chiu ; Lau, Tze K. ; Leung, Tse N. ; Lisa Y. S. Chan ; Cees B. M. Oudejans ; Ding, Chunming ; Y. M. Dennis Lo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c529t-a22a43daf025d0baedf164c90ff82ac333c526a99ff9e87f7641a74fd84c3d983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adult</topic><topic>Biological Sciences</topic><topic>Blood cells</topic><topic>Blood plasma</topic><topic>Cells</topic><topic>CpG Islands - genetics</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA - blood</topic><topic>DNA - metabolism</topic><topic>DNA Methylation</topic><topic>Epigenetics</topic><topic>Female</topic><topic>Fetus</topic><topic>Genes, Tumor Suppressor</topic><topic>Genetic Markers - genetics</topic><topic>Genetic Testing - methods</topic><topic>Genetics</topic><topic>Genotype</topic><topic>Genotypes</topic><topic>Humans</topic><topic>Methylation</topic><topic>Placenta</topic><topic>Placenta - metabolism</topic><topic>Plasma</topic><topic>Polymerase chain reaction</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Pregnancy</topic><topic>Prenatal Diagnosis</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Sequence Analysis, DNA</topic><topic>Serpins - blood</topic><topic>Serpins - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stephen S. C. Chim</creatorcontrib><creatorcontrib>Yu K. Tong</creatorcontrib><creatorcontrib>Rossa W. K. Chiu</creatorcontrib><creatorcontrib>Lau, Tze K.</creatorcontrib><creatorcontrib>Leung, Tse N.</creatorcontrib><creatorcontrib>Lisa Y. S. Chan</creatorcontrib><creatorcontrib>Cees B. M. Oudejans</creatorcontrib><creatorcontrib>Ding, Chunming</creatorcontrib><creatorcontrib>Y. M. Dennis Lo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stephen S. C. Chim</au><au>Yu K. Tong</au><au>Rossa W. K. Chiu</au><au>Lau, Tze K.</au><au>Leung, Tse N.</au><au>Lisa Y. S. Chan</au><au>Cees B. M. Oudejans</au><au>Ding, Chunming</au><au>Y. M. Dennis Lo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Detection of the Placental Epigenetic Signature of the Maspin Gene in Maternal Plasma</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2005-10-11</date><risdate>2005</risdate><volume>102</volume><issue>41</issue><spage>14753</spage><epage>14758</epage><pages>14753-14758</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>The discovery of fetal DNA in the plasma of pregnant women has opened up new approaches for noninvasive prenatal diagnosis and monitoring. Up to now, the lack of a fetal DNA marker that can be universally detected in maternal plasma has limited the clinical application of this technology. We hypothesized that epigenetic differences between the placenta and maternal blood cells could be used for developing such a marker. By using bisulfite DNA sequencing, the methylation status of the maspin gene promoter in placental tissues and paired maternal blood cells from pregnant women was analyzed. The maspin gene promoter was found to be hypomethylated in placental tissues and densely methylated in maternal blood cells. Genotyping of a single nucleotide polymorphism within the unmethylated maspin sequences in maternal plasma demonstrated that these sequences were derived from the fetus. By using real-time quantitative methylation-specific PCR, unmethylated maspin sequences were detected in maternal plasma in all three trimesters of pregnancy and were cleared within 24 h after delivery. The maternal plasma concentration of unmethylated maspin sequences was elevated by a median of 5.7 times in preeclamptic pregnancies compared with nonpreeclamptic pregnancies. Hypomethylated maspin DNA is the first universal marker for fetal DNA in maternal plasma, thus allowing the measurement of fetal DNA concentrations in pregnancy-associated disorders, irrespective of fetal gender and genetic polymorphisms. Differential DNA methylation between the placenta and maternal blood cells may be exploited to develop further markers for noninvasive prenatal assessment.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>16203989</pmid><doi>10.1073/pnas.0503335102</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2005-10, Vol.102 (41), p.14753-14758 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_pnas_primary_102_41_14753 |
| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Adult Biological Sciences Blood cells Blood plasma Cells CpG Islands - genetics Deoxyribonucleic acid DNA DNA - blood DNA - metabolism DNA Methylation Epigenetics Female Fetus Genes, Tumor Suppressor Genetic Markers - genetics Genetic Testing - methods Genetics Genotype Genotypes Humans Methylation Placenta Placenta - metabolism Plasma Polymerase chain reaction Polymorphism, Single Nucleotide Pregnancy Prenatal Diagnosis Promoter Regions, Genetic - genetics Reverse Transcriptase Polymerase Chain Reaction Sequence Analysis, DNA Serpins - blood Serpins - genetics |
| title | Detection of the Placental Epigenetic Signature of the Maspin Gene in Maternal Plasma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T00%3A07%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pnas_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Detection%20of%20the%20Placental%20Epigenetic%20Signature%20of%20the%20Maspin%20Gene%20in%20Maternal%20Plasma&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Stephen%20S.%20C.%20Chim&rft.date=2005-10-11&rft.volume=102&rft.issue=41&rft.spage=14753&rft.epage=14758&rft.pages=14753-14758&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.0503335102&rft_dat=%3Cjstor_pnas_%3E4143389%3C/jstor_pnas_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=201408751&rft_id=info:pmid/16203989&rft_jstor_id=4143389&rfr_iscdi=true |