Relationship between tumor DNA methylation status and patient characteristics in African-American and European-American women with breast cancer
Aberrant DNA methylation is critical for development and progression of breast cancer. We investigated the association of CpG island methylation in candidate genes and clinicopathological features in 65 African-American (AA) and European-American (EA) breast cancer patients. Quantitative methylation...
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| creator | Wang, Songping Dorsey, Tiffany H Terunuma, Atsushi Kittles, Rick A Ambs, Stefan Kwabi-Addo, Bernard |
| description | Aberrant DNA methylation is critical for development and progression of breast cancer. We investigated the association of CpG island methylation in candidate genes and clinicopathological features in 65 African-American (AA) and European-American (EA) breast cancer patients. Quantitative methylation analysis was carried out on bisulfite modified genomic DNA and sequencing (pyrosequencing) for promoter CpG islands of p16, ESR1, RASSF1A, RARβ2, CDH13, HIN1, SFRP1 genes and the LINE1 repetitive element using matched paired non-cancerous and breast tumor specimen (32 AA and 33 EA women). Five of the genes, all known tumor suppressor genes (RASSF1A, RARβ2, CDH13, HIN1 and SFRP1), were found to be frequently hypermethylated in breast tumor tissues but not in the adjacent non-cancerous tissues. Significant differences in the CDH13 methylation status were observed by comparing DNA methylation between AA and EA patients, with more obvious CDH13 methylation differences between the two patient groups in the ER- disease and among young patients (age |
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We investigated the association of CpG island methylation in candidate genes and clinicopathological features in 65 African-American (AA) and European-American (EA) breast cancer patients. Quantitative methylation analysis was carried out on bisulfite modified genomic DNA and sequencing (pyrosequencing) for promoter CpG islands of p16, ESR1, RASSF1A, RARβ2, CDH13, HIN1, SFRP1 genes and the LINE1 repetitive element using matched paired non-cancerous and breast tumor specimen (32 AA and 33 EA women). Five of the genes, all known tumor suppressor genes (RASSF1A, RARβ2, CDH13, HIN1 and SFRP1), were found to be frequently hypermethylated in breast tumor tissues but not in the adjacent non-cancerous tissues. Significant differences in the CDH13 methylation status were observed by comparing DNA methylation between AA and EA patients, with more obvious CDH13 methylation differences between the two patient groups in the ER- disease and among young patients (age<50). In addition, we observed associations between CDH13, SFRP1, and RASSF1A methylation and breast cancer subtypes and between SFRP1 methylation and patient's age. Furthermore, tumors that received neoadjuvant therapy tended to have reduced RASSF1A methylation when compared with chemotherapy naïve tumors. Finally, Kaplan Meier survival analysis showed a significant association between methylation at 3 loci (RASSF1A, RARβ2 and CDH13) and reduced overall disease survival. In conclusion, the DNA methylation status of breast tumors was found to be significantly associated with clinicopathological features and race/ethnicity of the patients.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0037928</identifier><identifier>PMID: 22701537</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aberration ; Adjuvant chemotherapy ; Adult ; African Americans ; African Americans - genetics ; Aged ; Analysis ; Biology ; Bisulfite ; Breast cancer ; Breast Neoplasms - genetics ; Cadherins - genetics ; Cancer ; Cancer patients ; Chemotherapy ; CpG islands ; CpG Islands - genetics ; Deoxyribonucleic acid ; Development and progression ; DNA ; DNA methylation ; DNA Methylation - genetics ; DNA sequencing ; Epigenetics ; ESR1 protein ; European Continental Ancestry Group - genetics ; Female ; Frizzled-related protein 1 ; Gene sequencing ; Genes ; Genetic research ; Humans ; Intercellular Signaling Peptides and Proteins - genetics ; Kaplan-Meier Estimate ; Medicine ; Membrane Proteins - genetics ; Methylation ; Middle Aged ; Minority & ethnic groups ; Mortality ; Mutation ; Patients ; Promoter Regions, Genetic - genetics ; Receptors, Retinoic Acid - genetics ; Socioeconomic factors ; Sulfites ; Survival ; Tissues ; Tumor suppressor genes ; Tumor Suppressor Proteins - genetics ; Tumors ; Womens health</subject><ispartof>PloS one, 2012-05, Vol.7 (5), p.e37928-e37928</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Wang et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-277143bf9859f785438d9a950ae8ef93d1cb882c47fdcd60a0af6da0880fa3993</citedby><cites>FETCH-LOGICAL-c692t-277143bf9859f785438d9a950ae8ef93d1cb882c47fdcd60a0af6da0880fa3993</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365111/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365111/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22701537$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Songping</creatorcontrib><creatorcontrib>Dorsey, Tiffany H</creatorcontrib><creatorcontrib>Terunuma, Atsushi</creatorcontrib><creatorcontrib>Kittles, Rick A</creatorcontrib><creatorcontrib>Ambs, Stefan</creatorcontrib><creatorcontrib>Kwabi-Addo, Bernard</creatorcontrib><title>Relationship between tumor DNA methylation status and patient characteristics in African-American and European-American women with breast cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Aberrant DNA methylation is critical for development and progression of breast cancer. We investigated the association of CpG island methylation in candidate genes and clinicopathological features in 65 African-American (AA) and European-American (EA) breast cancer patients. Quantitative methylation analysis was carried out on bisulfite modified genomic DNA and sequencing (pyrosequencing) for promoter CpG islands of p16, ESR1, RASSF1A, RARβ2, CDH13, HIN1, SFRP1 genes and the LINE1 repetitive element using matched paired non-cancerous and breast tumor specimen (32 AA and 33 EA women). Five of the genes, all known tumor suppressor genes (RASSF1A, RARβ2, CDH13, HIN1 and SFRP1), were found to be frequently hypermethylated in breast tumor tissues but not in the adjacent non-cancerous tissues. Significant differences in the CDH13 methylation status were observed by comparing DNA methylation between AA and EA patients, with more obvious CDH13 methylation differences between the two patient groups in the ER- disease and among young patients (age<50). In addition, we observed associations between CDH13, SFRP1, and RASSF1A methylation and breast cancer subtypes and between SFRP1 methylation and patient's age. Furthermore, tumors that received neoadjuvant therapy tended to have reduced RASSF1A methylation when compared with chemotherapy naïve tumors. Finally, Kaplan Meier survival analysis showed a significant association between methylation at 3 loci (RASSF1A, RARβ2 and CDH13) and reduced overall disease survival. In conclusion, the DNA methylation status of breast tumors was found to be significantly associated with clinicopathological features and race/ethnicity of the patients.</description><subject>Aberration</subject><subject>Adjuvant chemotherapy</subject><subject>Adult</subject><subject>African Americans</subject><subject>African Americans - genetics</subject><subject>Aged</subject><subject>Analysis</subject><subject>Biology</subject><subject>Bisulfite</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Cadherins - genetics</subject><subject>Cancer</subject><subject>Cancer patients</subject><subject>Chemotherapy</subject><subject>CpG islands</subject><subject>CpG Islands - genetics</subject><subject>Deoxyribonucleic acid</subject><subject>Development and progression</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>DNA Methylation - genetics</subject><subject>DNA sequencing</subject><subject>Epigenetics</subject><subject>ESR1 protein</subject><subject>European Continental Ancestry Group - genetics</subject><subject>Female</subject><subject>Frizzled-related protein 1</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Genetic research</subject><subject>Humans</subject><subject>Intercellular Signaling Peptides and Proteins - genetics</subject><subject>Kaplan-Meier Estimate</subject><subject>Medicine</subject><subject>Membrane Proteins - genetics</subject><subject>Methylation</subject><subject>Middle Aged</subject><subject>Minority & ethnic groups</subject><subject>Mortality</subject><subject>Mutation</subject><subject>Patients</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Receptors, Retinoic Acid - genetics</subject><subject>Socioeconomic factors</subject><subject>Sulfites</subject><subject>Survival</subject><subject>Tissues</subject><subject>Tumor suppressor genes</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>Tumors</subject><subject>Womens health</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9tu1DAQhiMEoqXwBggiISG42MWHxHFukFalwEoVlcrh1po4k41XSbzYDkvfgkfGe2i1i3qBfBFr8s0_nt-eJHlOyZTygr5b2tEN0E1XdsApIbwomXyQnNKSs4lghD882J8kT7xfEpJzKcTj5ISxgtCcF6fJn2vsIBg7-Nas0grDGnFIw9hbl374Mkt7DO3Njkh9gDD6FIY6XcUIDiHVLTjQAZ3xwWifmiGdNc5oGCazHrebLX8xOrvCw-ja9rHQ2oQ2rRyCj1owaHRPk0cNdB6f7b9nyfePF9_OP08urz7Nz2eXEy1KFiasKGjGq6aUedkUMs-4rEsocwIosSl5TXUlJdNZ0dS6FgQINKIGIiVpgJclP0te7nRXnfVqb6ZXlLOcsGhcHon5jqgtLNXKmR7cjbJg1DZg3UKBi113qDijiLIqBakwQ82kyCsi8ngaWedZxqLW-321seqx1tE7B92R6PGfwbRqYX8pzkVOKY0Cb_YCzv4c0QfVG6-x62BAO8ZzE0YkJ4RuOnv1D3p_d3tqAbEBMzQ21tUbUTXLClFKIQWJ1PQeKq4ae6Pjy2tMjB8lvD1KiEzA32EBo_dq_vX6_9mrH8fs6wO2RehC6203bp_uMZjtQO2s9w6bO5MpUZvBuXVDbQZH7Qcnpr04vKC7pNtJ4X8Bu_sVFQ</recordid><startdate>20120531</startdate><enddate>20120531</enddate><creator>Wang, Songping</creator><creator>Dorsey, Tiffany H</creator><creator>Terunuma, Atsushi</creator><creator>Kittles, Rick A</creator><creator>Ambs, Stefan</creator><creator>Kwabi-Addo, Bernard</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20120531</creationdate><title>Relationship between tumor DNA methylation status and patient characteristics in African-American and European-American women with breast cancer</title><author>Wang, Songping ; Dorsey, Tiffany H ; Terunuma, Atsushi ; Kittles, Rick A ; Ambs, Stefan ; Kwabi-Addo, Bernard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-277143bf9859f785438d9a950ae8ef93d1cb882c47fdcd60a0af6da0880fa3993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Aberration</topic><topic>Adjuvant chemotherapy</topic><topic>Adult</topic><topic>African Americans</topic><topic>African Americans - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Songping</au><au>Dorsey, Tiffany H</au><au>Terunuma, Atsushi</au><au>Kittles, Rick A</au><au>Ambs, Stefan</au><au>Kwabi-Addo, Bernard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Relationship between tumor DNA methylation status and patient characteristics in African-American and European-American women with breast cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-05-31</date><risdate>2012</risdate><volume>7</volume><issue>5</issue><spage>e37928</spage><epage>e37928</epage><pages>e37928-e37928</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Aberrant DNA methylation is critical for development and progression of breast cancer. We investigated the association of CpG island methylation in candidate genes and clinicopathological features in 65 African-American (AA) and European-American (EA) breast cancer patients. Quantitative methylation analysis was carried out on bisulfite modified genomic DNA and sequencing (pyrosequencing) for promoter CpG islands of p16, ESR1, RASSF1A, RARβ2, CDH13, HIN1, SFRP1 genes and the LINE1 repetitive element using matched paired non-cancerous and breast tumor specimen (32 AA and 33 EA women). Five of the genes, all known tumor suppressor genes (RASSF1A, RARβ2, CDH13, HIN1 and SFRP1), were found to be frequently hypermethylated in breast tumor tissues but not in the adjacent non-cancerous tissues. Significant differences in the CDH13 methylation status were observed by comparing DNA methylation between AA and EA patients, with more obvious CDH13 methylation differences between the two patient groups in the ER- disease and among young patients (age<50). In addition, we observed associations between CDH13, SFRP1, and RASSF1A methylation and breast cancer subtypes and between SFRP1 methylation and patient's age. Furthermore, tumors that received neoadjuvant therapy tended to have reduced RASSF1A methylation when compared with chemotherapy naïve tumors. Finally, Kaplan Meier survival analysis showed a significant association between methylation at 3 loci (RASSF1A, RARβ2 and CDH13) and reduced overall disease survival. In conclusion, the DNA methylation status of breast tumors was found to be significantly associated with clinicopathological features and race/ethnicity of the patients.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22701537</pmid><doi>10.1371/journal.pone.0037928</doi><tpages>e37928</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2012-05, Vol.7 (5), p.e37928-e37928 |
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| language | eng |
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| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Aberration Adjuvant chemotherapy Adult African Americans African Americans - genetics Aged Analysis Biology Bisulfite Breast cancer Breast Neoplasms - genetics Cadherins - genetics Cancer Cancer patients Chemotherapy CpG islands CpG Islands - genetics Deoxyribonucleic acid Development and progression DNA DNA methylation DNA Methylation - genetics DNA sequencing Epigenetics ESR1 protein European Continental Ancestry Group - genetics Female Frizzled-related protein 1 Gene sequencing Genes Genetic research Humans Intercellular Signaling Peptides and Proteins - genetics Kaplan-Meier Estimate Medicine Membrane Proteins - genetics Methylation Middle Aged Minority & ethnic groups Mortality Mutation Patients Promoter Regions, Genetic - genetics Receptors, Retinoic Acid - genetics Socioeconomic factors Sulfites Survival Tissues Tumor suppressor genes Tumor Suppressor Proteins - genetics Tumors Womens health |
| title | Relationship between tumor DNA methylation status and patient characteristics in African-American and European-American women with breast cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T20%3A12%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Relationship%20between%20tumor%20DNA%20methylation%20status%20and%20patient%20characteristics%20in%20African-American%20and%20European-American%20women%20with%20breast%20cancer&rft.jtitle=PloS%20one&rft.au=Wang,%20Songping&rft.date=2012-05-31&rft.volume=7&rft.issue=5&rft.spage=e37928&rft.epage=e37928&rft.pages=e37928-e37928&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0037928&rft_dat=%3Cgale_plos_%3EA476986860%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1325021935&rft_id=info:pmid/22701537&rft_galeid=A476986860&rft_doaj_id=oai_doaj_org_article_321ee8b960be4ec2865b06550a8d5442&rfr_iscdi=true |