MGMT promoter methylation in triple negative breast cancer of the GeparSixto trial
Triple-negative breast cancer (TNBC) is typically treated with chemotherapeutic agents, including carboplatin (Cb), an DNA platinating agent. The O6-methylguanine-DNA-methyltransferase gene (MGMT) encodes for the protein O6-alkylguanine-DNA-alkyltransferase (MGMT protein). MGMT protein is involved i...
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| creator | Jank, Paul Gehlhaar, Claire Bianca, Lederer Caterina, Fontanella Andreas, Schneeweiss Karn, Thomas Marmé, Frederik Sinn, Hans-Peter van Mackelenbergh, Marion Sinn, Bruno Zahm, Dirk-Michael Ingold-Heppner, Barbara Schem, Christian Stickeler, Elmar Fasching, Peter A Nekljudova, Valentina Taube, Eliane Tabea Heppner, Frank Müller, Volkmar Denkert, Carsten Loibl, Sibylle |
| description | Triple-negative breast cancer (TNBC) is typically treated with chemotherapeutic agents, including carboplatin (Cb), an DNA platinating agent. The O6-methylguanine-DNA-methyltransferase gene (MGMT) encodes for the protein O6-alkylguanine-DNA-alkyltransferase (MGMT protein). MGMT protein is involved in DNA repair mechanisms to remove mutagenic and cytotoxic adducts from O6-guanine in DNA. In glioblastoma multiforme, MGMT methylation status is a predictive biomarker for increased response to temozolomide therapy. It has been suggested, that MGMT protein may have relevance for cellular adaptation and could have an influence on resistance to carboplatin therapy. We investigated the influence of MGMT promoter methylation on pathologic complete response and survival of patients with TNBC treated in the neoadjuvant GeparSixto trial. In 174 of 210 available TNBC tumors a valid MGMT promoter methylation status was determined by pyrosequencing of 5 CpG islands. In 21.8%, we detected a mean MGMT promoter methylation >10%. Overall, MGMT promoter methylation was not significantly associated with pathological complete response (pCR) rate. After stratification for the two therapy arms with and without Cb no statistically significant differences in therapy response rates between the two MGMT promoter methylation groups could be observed. Our results show that different MGMT promoter methylation status is not related to different chemotherapy response rates in the TNBC setting in GeparSixto. |
| doi_str_mv | 10.1371/journal.pone.0238021 |
| format | Article |
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The O6-methylguanine-DNA-methyltransferase gene (MGMT) encodes for the protein O6-alkylguanine-DNA-alkyltransferase (MGMT protein). MGMT protein is involved in DNA repair mechanisms to remove mutagenic and cytotoxic adducts from O6-guanine in DNA. In glioblastoma multiforme, MGMT methylation status is a predictive biomarker for increased response to temozolomide therapy. It has been suggested, that MGMT protein may have relevance for cellular adaptation and could have an influence on resistance to carboplatin therapy. We investigated the influence of MGMT promoter methylation on pathologic complete response and survival of patients with TNBC treated in the neoadjuvant GeparSixto trial. In 174 of 210 available TNBC tumors a valid MGMT promoter methylation status was determined by pyrosequencing of 5 CpG islands. In 21.8%, we detected a mean MGMT promoter methylation >10%. Overall, MGMT promoter methylation was not significantly associated with pathological complete response (pCR) rate. After stratification for the two therapy arms with and without Cb no statistically significant differences in therapy response rates between the two MGMT promoter methylation groups could be observed. Our results show that different MGMT promoter methylation status is not related to different chemotherapy response rates in the TNBC setting in GeparSixto.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0238021</identifier><identifier>PMID: 32841306</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Adducts ; Biology and life sciences ; Biomarkers ; Biopsy ; Brain cancer ; Breast cancer ; Cancer therapies ; Carboplatin ; Care and treatment ; Chemotherapy ; Clinical trials ; CpG islands ; Cytotoxicity ; Deoxyribonucleic acid ; Development and progression ; DNA ; DNA alkyltransferase ; DNA methylation ; DNA methyltransferase ; DNA repair ; Epigenetics ; Genetic aspects ; Glioblastoma ; Glioblastoma multiforme ; Guanine ; Health aspects ; Medicine and Health Sciences ; Methylation ; Methylguanine ; O6-methylguanine-DNA methyltransferase ; Physical Sciences ; Promoters (Genetics) ; Proteins ; Research and Analysis Methods ; Statistical analysis ; Temozolomide ; Triple negative breast cancer ; Tumors</subject><ispartof>PloS one, 2020-08, Vol.15 (8), p.e0238021</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Jank et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://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. 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The O6-methylguanine-DNA-methyltransferase gene (MGMT) encodes for the protein O6-alkylguanine-DNA-alkyltransferase (MGMT protein). MGMT protein is involved in DNA repair mechanisms to remove mutagenic and cytotoxic adducts from O6-guanine in DNA. In glioblastoma multiforme, MGMT methylation status is a predictive biomarker for increased response to temozolomide therapy. It has been suggested, that MGMT protein may have relevance for cellular adaptation and could have an influence on resistance to carboplatin therapy. We investigated the influence of MGMT promoter methylation on pathologic complete response and survival of patients with TNBC treated in the neoadjuvant GeparSixto trial. In 174 of 210 available TNBC tumors a valid MGMT promoter methylation status was determined by pyrosequencing of 5 CpG islands. In 21.8%, we detected a mean MGMT promoter methylation >10%. Overall, MGMT promoter methylation was not significantly associated with pathological complete response (pCR) rate. After stratification for the two therapy arms with and without Cb no statistically significant differences in therapy response rates between the two MGMT promoter methylation groups could be observed. Our results show that different MGMT promoter methylation status is not related to different chemotherapy response rates in the TNBC setting in GeparSixto.</description><subject>Adducts</subject><subject>Biology and life sciences</subject><subject>Biomarkers</subject><subject>Biopsy</subject><subject>Brain cancer</subject><subject>Breast cancer</subject><subject>Cancer therapies</subject><subject>Carboplatin</subject><subject>Care and treatment</subject><subject>Chemotherapy</subject><subject>Clinical trials</subject><subject>CpG islands</subject><subject>Cytotoxicity</subject><subject>Deoxyribonucleic acid</subject><subject>Development and progression</subject><subject>DNA</subject><subject>DNA alkyltransferase</subject><subject>DNA methylation</subject><subject>DNA methyltransferase</subject><subject>DNA repair</subject><subject>Epigenetics</subject><subject>Genetic aspects</subject><subject>Glioblastoma</subject><subject>Glioblastoma multiforme</subject><subject>Guanine</subject><subject>Health aspects</subject><subject>Medicine and Health Sciences</subject><subject>Methylation</subject><subject>Methylguanine</subject><subject>O6-methylguanine-DNA methyltransferase</subject><subject>Physical Sciences</subject><subject>Promoters (Genetics)</subject><subject>Proteins</subject><subject>Research and Analysis Methods</subject><subject>Statistical analysis</subject><subject>Temozolomide</subject><subject>Triple negative breast 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promoter methylation in triple negative breast cancer of the GeparSixto trial</title><author>Jank, Paul ; Gehlhaar, Claire ; Bianca, Lederer ; Caterina, Fontanella ; Andreas, Schneeweiss ; Karn, Thomas ; Marmé, Frederik ; Sinn, Hans-Peter ; van Mackelenbergh, Marion ; Sinn, Bruno ; Zahm, Dirk-Michael ; Ingold-Heppner, Barbara ; Schem, Christian ; Stickeler, Elmar ; Fasching, Peter A ; Nekljudova, Valentina ; Taube, Eliane Tabea ; Heppner, Frank ; Müller, Volkmar ; Denkert, Carsten ; Loibl, Sibylle</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5841-511096f3acd82beb7244557831f6de4686b56fe945929e685d8546b7ba5583433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adducts</topic><topic>Biology and life sciences</topic><topic>Biomarkers</topic><topic>Biopsy</topic><topic>Brain cancer</topic><topic>Breast cancer</topic><topic>Cancer 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A</au><au>Nekljudova, Valentina</au><au>Taube, Eliane Tabea</au><au>Heppner, Frank</au><au>Müller, Volkmar</au><au>Denkert, Carsten</au><au>Loibl, Sibylle</au><au>Banerjee, Sushanta K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MGMT promoter methylation in triple negative breast cancer of the GeparSixto trial</atitle><jtitle>PloS one</jtitle><date>2020-08-25</date><risdate>2020</risdate><volume>15</volume><issue>8</issue><spage>e0238021</spage><pages>e0238021-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Triple-negative breast cancer (TNBC) is typically treated with chemotherapeutic agents, including carboplatin (Cb), an DNA platinating agent. The O6-methylguanine-DNA-methyltransferase gene (MGMT) encodes for the protein O6-alkylguanine-DNA-alkyltransferase (MGMT protein). MGMT protein is involved in DNA repair mechanisms to remove mutagenic and cytotoxic adducts from O6-guanine in DNA. In glioblastoma multiforme, MGMT methylation status is a predictive biomarker for increased response to temozolomide therapy. It has been suggested, that MGMT protein may have relevance for cellular adaptation and could have an influence on resistance to carboplatin therapy. We investigated the influence of MGMT promoter methylation on pathologic complete response and survival of patients with TNBC treated in the neoadjuvant GeparSixto trial. In 174 of 210 available TNBC tumors a valid MGMT promoter methylation status was determined by pyrosequencing of 5 CpG islands. In 21.8%, we detected a mean MGMT promoter methylation >10%. Overall, MGMT promoter methylation was not significantly associated with pathological complete response (pCR) rate. After stratification for the two therapy arms with and without Cb no statistically significant differences in therapy response rates between the two MGMT promoter methylation groups could be observed. Our results show that different MGMT promoter methylation status is not related to different chemotherapy response rates in the TNBC setting in GeparSixto.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>32841306</pmid><doi>10.1371/journal.pone.0238021</doi><tpages>e0238021</tpages><orcidid>https://orcid.org/0000-0002-4512-2226</orcidid><orcidid>https://orcid.org/0000-0001-7076-0476</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2020-08, Vol.15 (8), p.e0238021 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2437105661 |
| source | DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adducts Biology and life sciences Biomarkers Biopsy Brain cancer Breast cancer Cancer therapies Carboplatin Care and treatment Chemotherapy Clinical trials CpG islands Cytotoxicity Deoxyribonucleic acid Development and progression DNA DNA alkyltransferase DNA methylation DNA methyltransferase DNA repair Epigenetics Genetic aspects Glioblastoma Glioblastoma multiforme Guanine Health aspects Medicine and Health Sciences Methylation Methylguanine O6-methylguanine-DNA methyltransferase Physical Sciences Promoters (Genetics) Proteins Research and Analysis Methods Statistical analysis Temozolomide Triple negative breast cancer Tumors |
| title | MGMT promoter methylation in triple negative breast cancer of the GeparSixto trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-19T06%3A23%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=MGMT%20promoter%20methylation%20in%20triple%20negative%20breast%20cancer%20of%20the%20GeparSixto%20trial&rft.jtitle=PloS%20one&rft.au=Jank,%20Paul&rft.date=2020-08-25&rft.volume=15&rft.issue=8&rft.spage=e0238021&rft.pages=e0238021-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0238021&rft_dat=%3Cgale_plos_%3EA633501043%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=2437105661&rft_id=info:pmid/32841306&rft_galeid=A633501043&rft_doaj_id=oai_doaj_org_article_57023619e9d140768d447fde0e25eade&rfr_iscdi=true |