Quantitative analysis of associations between DNA hypermethylation, hypomethylation, and DNMT RNA levels in ovarian tumors
How hypermethylation and hypomethylation of different parts of the genome in cancer are related to each other and to DNA methyltransferase (DNMT) gene expression is ill defined. We used ovarian epithelial tumors of different malignant potential to look for associations between 5′-gene region or prom...
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| Veröffentlicht in: | Oncogene 2006-04, Vol.25 (18), p.2636-2645 |
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| creator | Ehrlich, M Woods, C B Yu, M C Dubeau, L Yang, F Campan, M Weisenberger, D J Long, Ti Youn, B Fiala, E S Laird, P W |
| description | How hypermethylation and hypomethylation of different parts of the genome in cancer are related to each other and to DNA methyltransferase (DNMT) gene expression is ill defined. We used ovarian epithelial tumors of different malignant potential to look for associations between 5′-gene region or promoter hypermethylation, satellite, or global DNA hypomethylation, and RNA levels for ten DNMT isoforms. In the quantitative MethyLight assay, six of the 55 examined gene loci (
LTB4R, MTHFR, CDH13, PGR, CDH1,
and
IGSF4)
were significantly hypermethylated relative to the degree of malignancy (after adjustment for multiple comparisons;
P |
| doi_str_mv | 10.1038/sj.onc.1209145 |
| format | Article |
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LTB4R, MTHFR, CDH13, PGR, CDH1,
and
IGSF4)
were significantly hypermethylated relative to the degree of malignancy (after adjustment for multiple comparisons;
P
<0.001). Importantly, hypermethylation of these genes was associated with degree of malignancy independently of the association of satellite or global DNA hypomethylation with degree of malignancy. Cancer-related increases in methylation of only two studied genes,
LTB4R
and
MTHFR,
which were appreciably methylated even in control tissues, were associated with DNMT1 RNA levels. Cancer-linked satellite DNA hypomethylation was independent of RNA levels for all DNMT3B isoforms, despite the ICF syndrome-linked DNMT3B deficiency causing juxtacentromeric satellite DNA hypomethylation. Our results suggest that there is not a simple association of gene hypermethylation in cancer with altered DNMT RNA levels, and that this hypermethylation is neither the result nor the cause of satellite and global DNA hypomethylation.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/sj.onc.1209145</identifier><identifier>PMID: 16532039</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adenocarcinoma, Mucinous - genetics ; Adenocarcinoma, Mucinous - pathology ; Adolescent ; Adult ; Aged ; Apoptosis ; Biological and medical sciences ; Cancer ; Carcinoma, Endometrioid - genetics ; Carcinoma, Endometrioid - pathology ; Cell Biology ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Cystadenoma, Serous - genetics ; Cystadenoma, Serous - pathology ; Deoxyribonucleic acid ; DNA ; DNA (Cytosine-5-)-Methyltransferase 1 ; DNA (Cytosine-5-)-Methyltransferases - genetics ; DNA Methylation ; DNA methyltransferase ; DNA, Neoplasm ; DNMT1 protein ; E-cadherin ; Female ; Female genital diseases ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genomes ; Gynecology. Andrology. Obstetrics ; Human Genetics ; Humans ; ICF syndrome ; Internal Medicine ; Isoforms ; Malignancy ; Medical sciences ; Medicine ; Medicine & Public Health ; Methylenetetrahydrofolate reductase ; Middle Aged ; Molecular and cellular biology ; Neoplasm Proteins - genetics ; Oncology ; original-article ; Ovarian cancer ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - pathology ; Ovaries ; Quantitative analysis ; Ribonucleic acid ; RNA ; RNA, Neoplasm - genetics ; RNA, Neoplasm - metabolism ; Satellite DNA ; Satellite RNA ; Tumor Suppressor Proteins ; Tumors</subject><ispartof>Oncogene, 2006-04, Vol.25 (18), p.2636-2645</ispartof><rights>Springer Nature Limited 2006</rights><rights>2006 INIST-CNRS</rights><rights>COPYRIGHT 2006 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Apr 27, 2006</rights><rights>Nature Publishing Group 2006.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c649t-b08f81f506a8ade5f4c338d80ab53cdc82d835c9788412fcba55ae0c3bff16623</citedby><cites>FETCH-LOGICAL-c649t-b08f81f506a8ade5f4c338d80ab53cdc82d835c9788412fcba55ae0c3bff16623</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.onc.1209145$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.onc.1209145$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17728960$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16532039$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ehrlich, M</creatorcontrib><creatorcontrib>Woods, C B</creatorcontrib><creatorcontrib>Yu, M C</creatorcontrib><creatorcontrib>Dubeau, L</creatorcontrib><creatorcontrib>Yang, F</creatorcontrib><creatorcontrib>Campan, M</creatorcontrib><creatorcontrib>Weisenberger, D J</creatorcontrib><creatorcontrib>Long, Ti</creatorcontrib><creatorcontrib>Youn, B</creatorcontrib><creatorcontrib>Fiala, E S</creatorcontrib><creatorcontrib>Laird, P W</creatorcontrib><title>Quantitative analysis of associations between DNA hypermethylation, hypomethylation, and DNMT RNA levels in ovarian tumors</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>How hypermethylation and hypomethylation of different parts of the genome in cancer are related to each other and to DNA methyltransferase (DNMT) gene expression is ill defined. We used ovarian epithelial tumors of different malignant potential to look for associations between 5′-gene region or promoter hypermethylation, satellite, or global DNA hypomethylation, and RNA levels for ten DNMT isoforms. In the quantitative MethyLight assay, six of the 55 examined gene loci (
LTB4R, MTHFR, CDH13, PGR, CDH1,
and
IGSF4)
were significantly hypermethylated relative to the degree of malignancy (after adjustment for multiple comparisons;
P
<0.001). Importantly, hypermethylation of these genes was associated with degree of malignancy independently of the association of satellite or global DNA hypomethylation with degree of malignancy. Cancer-related increases in methylation of only two studied genes,
LTB4R
and
MTHFR,
which were appreciably methylated even in control tissues, were associated with DNMT1 RNA levels. Cancer-linked satellite DNA hypomethylation was independent of RNA levels for all DNMT3B isoforms, despite the ICF syndrome-linked DNMT3B deficiency causing juxtacentromeric satellite DNA hypomethylation. Our results suggest that there is not a simple association of gene hypermethylation in cancer with altered DNMT RNA levels, and that this hypermethylation is neither the result nor the cause of satellite and global DNA hypomethylation.</description><subject>Adenocarcinoma, Mucinous - genetics</subject><subject>Adenocarcinoma, Mucinous - pathology</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Cancer</subject><subject>Carcinoma, Endometrioid - genetics</subject><subject>Carcinoma, Endometrioid - pathology</subject><subject>Cell Biology</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Cystadenoma, Serous - genetics</subject><subject>Cystadenoma, Serous - pathology</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA (Cytosine-5-)-Methyltransferase 1</subject><subject>DNA (Cytosine-5-)-Methyltransferases - genetics</subject><subject>DNA Methylation</subject><subject>DNA methyltransferase</subject><subject>DNA, Neoplasm</subject><subject>DNMT1 protein</subject><subject>E-cadherin</subject><subject>Female</subject><subject>Female genital diseases</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genomes</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>ICF syndrome</subject><subject>Internal Medicine</subject><subject>Isoforms</subject><subject>Malignancy</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Methylenetetrahydrofolate reductase</subject><subject>Middle Aged</subject><subject>Molecular and cellular biology</subject><subject>Neoplasm Proteins - genetics</subject><subject>Oncology</subject><subject>original-article</subject><subject>Ovarian cancer</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Ovaries</subject><subject>Quantitative analysis</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Neoplasm - genetics</subject><subject>RNA, Neoplasm - metabolism</subject><subject>Satellite DNA</subject><subject>Satellite RNA</subject><subject>Tumor Suppressor Proteins</subject><subject>Tumors</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkt2LEzEUxQdR3Lr66qMMij7Zbj4mk-RFKOsnrIqyPoc7maRNmUlqMlOpf72pHawrLJKHwLm_e5N7OEXxGKMFRlRcpM0ieL3ABElcsTvFDFe8njMmq7vFDEmG5pJQclY8SGmDEOISkfvFGa4ZJYjKWfHzywh-cAMMbmdK8NDtk0tlsCWkFLTLevCpbMzwwxhfvv60LNf7rYm9Gdb77nf15UEJNwTwbUY_XpdfM9-ZnelS6XwZdhAd-HIY-xDTw-KehS6ZR9N9Xnx7--b68v386vO7D5fLq7muKznMGySswJahGgS0htlKUypagaBhVLdakFZQpiUXosLE6gYYA4M0bazFdU3oefHqOHc7Nr1ptfFDhE5to-sh7lUAp25WvFurVdgpXFVS8MOAF9OAGL6PJg2qd0mbrgNvwphUnV1lFab_BbHklGDGM_jsH3ATxpjNT4rUeRJjnNSZenorRTitJJY4Q4sjtILOKOdtyDvofFrTOx28sS7rSyzyH2vK-alBx5BSNPaPExipQ6ZU2qicKTVlKjc8-du_Ez6FKAPPJwCShs5G8NqlE8c5EbJGmbs4cimX_MrE0z63PP0L0EnmwA</recordid><startdate>20060427</startdate><enddate>20060427</enddate><creator>Ehrlich, M</creator><creator>Woods, C B</creator><creator>Yu, M C</creator><creator>Dubeau, L</creator><creator>Yang, F</creator><creator>Campan, M</creator><creator>Weisenberger, D J</creator><creator>Long, Ti</creator><creator>Youn, B</creator><creator>Fiala, E S</creator><creator>Laird, P W</creator><general>Nature Publishing Group UK</general><general>Nature Publishing</general><general>Nature Publishing Group</general><scope>IQODW</scope><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>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20060427</creationdate><title>Quantitative analysis of associations between DNA hypermethylation, hypomethylation, and DNMT RNA levels in ovarian tumors</title><author>Ehrlich, M ; Woods, C B ; Yu, M C ; Dubeau, L ; Yang, F ; Campan, M ; Weisenberger, D J ; Long, Ti ; Youn, B ; Fiala, E S ; Laird, P W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c649t-b08f81f506a8ade5f4c338d80ab53cdc82d835c9788412fcba55ae0c3bff16623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adenocarcinoma, Mucinous - genetics</topic><topic>Adenocarcinoma, Mucinous - pathology</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>Cancer</topic><topic>Carcinoma, Endometrioid - genetics</topic><topic>Carcinoma, Endometrioid - pathology</topic><topic>Cell Biology</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Cystadenoma, Serous - genetics</topic><topic>Cystadenoma, Serous - pathology</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA (Cytosine-5-)-Methyltransferase 1</topic><topic>DNA (Cytosine-5-)-Methyltransferases - genetics</topic><topic>DNA Methylation</topic><topic>DNA methyltransferase</topic><topic>DNA, Neoplasm</topic><topic>DNMT1 protein</topic><topic>E-cadherin</topic><topic>Female</topic><topic>Female genital diseases</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genomes</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>ICF syndrome</topic><topic>Internal Medicine</topic><topic>Isoforms</topic><topic>Malignancy</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Methylenetetrahydrofolate reductase</topic><topic>Middle Aged</topic><topic>Molecular and cellular biology</topic><topic>Neoplasm Proteins - genetics</topic><topic>Oncology</topic><topic>original-article</topic><topic>Ovarian cancer</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Ovaries</topic><topic>Quantitative analysis</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Neoplasm - genetics</topic><topic>RNA, Neoplasm - metabolism</topic><topic>Satellite DNA</topic><topic>Satellite RNA</topic><topic>Tumor Suppressor Proteins</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ehrlich, M</creatorcontrib><creatorcontrib>Woods, C B</creatorcontrib><creatorcontrib>Yu, M C</creatorcontrib><creatorcontrib>Dubeau, L</creatorcontrib><creatorcontrib>Yang, F</creatorcontrib><creatorcontrib>Campan, M</creatorcontrib><creatorcontrib>Weisenberger, D J</creatorcontrib><creatorcontrib>Long, Ti</creatorcontrib><creatorcontrib>Youn, B</creatorcontrib><creatorcontrib>Fiala, E S</creatorcontrib><creatorcontrib>Laird, P W</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ehrlich, M</au><au>Woods, C B</au><au>Yu, M C</au><au>Dubeau, L</au><au>Yang, F</au><au>Campan, M</au><au>Weisenberger, D J</au><au>Long, Ti</au><au>Youn, B</au><au>Fiala, E S</au><au>Laird, P W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Quantitative analysis of associations between DNA hypermethylation, hypomethylation, and DNMT RNA levels in ovarian tumors</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2006-04-27</date><risdate>2006</risdate><volume>25</volume><issue>18</issue><spage>2636</spage><epage>2645</epage><pages>2636-2645</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>How hypermethylation and hypomethylation of different parts of the genome in cancer are related to each other and to DNA methyltransferase (DNMT) gene expression is ill defined. We used ovarian epithelial tumors of different malignant potential to look for associations between 5′-gene region or promoter hypermethylation, satellite, or global DNA hypomethylation, and RNA levels for ten DNMT isoforms. In the quantitative MethyLight assay, six of the 55 examined gene loci (
LTB4R, MTHFR, CDH13, PGR, CDH1,
and
IGSF4)
were significantly hypermethylated relative to the degree of malignancy (after adjustment for multiple comparisons;
P
<0.001). Importantly, hypermethylation of these genes was associated with degree of malignancy independently of the association of satellite or global DNA hypomethylation with degree of malignancy. Cancer-related increases in methylation of only two studied genes,
LTB4R
and
MTHFR,
which were appreciably methylated even in control tissues, were associated with DNMT1 RNA levels. Cancer-linked satellite DNA hypomethylation was independent of RNA levels for all DNMT3B isoforms, despite the ICF syndrome-linked DNMT3B deficiency causing juxtacentromeric satellite DNA hypomethylation. Our results suggest that there is not a simple association of gene hypermethylation in cancer with altered DNMT RNA levels, and that this hypermethylation is neither the result nor the cause of satellite and global DNA hypomethylation.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>16532039</pmid><doi>10.1038/sj.onc.1209145</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenocarcinoma, Mucinous - genetics Adenocarcinoma, Mucinous - pathology Adolescent Adult Aged Apoptosis Biological and medical sciences Cancer Carcinoma, Endometrioid - genetics Carcinoma, Endometrioid - pathology Cell Biology Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cystadenoma, Serous - genetics Cystadenoma, Serous - pathology Deoxyribonucleic acid DNA DNA (Cytosine-5-)-Methyltransferase 1 DNA (Cytosine-5-)-Methyltransferases - genetics DNA Methylation DNA methyltransferase DNA, Neoplasm DNMT1 protein E-cadherin Female Female genital diseases Fundamental and applied biological sciences. Psychology Gene expression Gene Expression Regulation, Neoplastic Genomes Gynecology. Andrology. Obstetrics Human Genetics Humans ICF syndrome Internal Medicine Isoforms Malignancy Medical sciences Medicine Medicine & Public Health Methylenetetrahydrofolate reductase Middle Aged Molecular and cellular biology Neoplasm Proteins - genetics Oncology original-article Ovarian cancer Ovarian Neoplasms - genetics Ovarian Neoplasms - pathology Ovaries Quantitative analysis Ribonucleic acid RNA RNA, Neoplasm - genetics RNA, Neoplasm - metabolism Satellite DNA Satellite RNA Tumor Suppressor Proteins Tumors |
| title | Quantitative analysis of associations between DNA hypermethylation, hypomethylation, and DNMT RNA levels in ovarian tumors |
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