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MGMT promoter methylation in triple negative breast cancer of the GeparSixto trial

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MGMT promoter methylation in triple negative breast cancer of the GeparSixto trial. / 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.

in: PLOS ONE, Jahrgang 15, Nr. 8, 2020, S. e0238021.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Jank, P, Gehlhaar, C, Bianca, L, Caterina, F, Andreas, S, Karn, T, Marmé, F, Sinn, H-P, van Mackelenbergh, M, Sinn, B, Zahm, D-M, Ingold-Heppner, B, Schem, C, Stickeler, E, Fasching, PA, Nekljudova, V, Taube, ET, Heppner, F, Müller, V, Denkert, C & Loibl, S 2020, 'MGMT promoter methylation in triple negative breast cancer of the GeparSixto trial', PLOS ONE, Jg. 15, Nr. 8, S. e0238021. https://doi.org/10.1371/journal.pone.0238021

APA

Jank, P., Gehlhaar, C., Bianca, L., Caterina, F., Andreas, S., Karn, T., Marmé, F., Sinn, H-P., van Mackelenbergh, M., Sinn, B., Zahm, D-M., Ingold-Heppner, B., Schem, C., Stickeler, E., Fasching, P. A., Nekljudova, V., Taube, E. T., Heppner, F., Müller, V., ... Loibl, S. (2020). MGMT promoter methylation in triple negative breast cancer of the GeparSixto trial. PLOS ONE, 15(8), e0238021. https://doi.org/10.1371/journal.pone.0238021

Vancouver

Jank P, Gehlhaar C, Bianca L, Caterina F, Andreas S, Karn T et al. MGMT promoter methylation in triple negative breast cancer of the GeparSixto trial. PLOS ONE. 2020;15(8):e0238021. https://doi.org/10.1371/journal.pone.0238021

Bibtex

@article{3bef8b05392b44b587a283c5771b2bf4,
title = "MGMT promoter methylation in triple negative breast cancer of the GeparSixto trial",
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.",
keywords = "Biopsy, Clinical Trials as Topic, Clinical Trials, Phase II as Topic, Cohort Studies, CpG Islands/genetics, DNA Methylation, DNA Modification Methylases/genetics, DNA Repair Enzymes/genetics, Humans, Promoter Regions, Genetic/genetics, Retrospective Studies, Sequence Analysis, DNA, Survival Analysis, Triple Negative Breast Neoplasms/genetics, Tumor Suppressor Proteins/genetics",
author = "Paul Jank and Claire Gehlhaar and Lederer Bianca and Fontanella Caterina and Schneeweiss Andreas and Thomas Karn and Frederik Marm{\'e} and Hans-Peter Sinn and {van Mackelenbergh}, Marion and Bruno Sinn and Dirk-Michael Zahm and Barbara Ingold-Heppner and Christian Schem and Elmar Stickeler and Fasching, {Peter A} and Valentina Nekljudova and Taube, {Eliane Tabea} and Frank Heppner and Volkmar M{\"u}ller and Carsten Denkert and Sibylle Loibl",
year = "2020",
doi = "10.1371/journal.pone.0238021",
language = "English",
volume = "15",
pages = "e0238021",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "8",

}

RIS

TY - JOUR

T1 - MGMT promoter methylation in triple negative breast cancer of the GeparSixto trial

AU - Jank, Paul

AU - Gehlhaar, Claire

AU - Bianca, Lederer

AU - Caterina, Fontanella

AU - Andreas, Schneeweiss

AU - Karn, Thomas

AU - Marmé, Frederik

AU - Sinn, Hans-Peter

AU - van Mackelenbergh, Marion

AU - Sinn, Bruno

AU - Zahm, Dirk-Michael

AU - Ingold-Heppner, Barbara

AU - Schem, Christian

AU - Stickeler, Elmar

AU - Fasching, Peter A

AU - Nekljudova, Valentina

AU - Taube, Eliane Tabea

AU - Heppner, Frank

AU - Müller, Volkmar

AU - Denkert, Carsten

AU - Loibl, Sibylle

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Biopsy

KW - Clinical Trials as Topic

KW - Clinical Trials, Phase II as Topic

KW - Cohort Studies

KW - CpG Islands/genetics

KW - DNA Methylation

KW - DNA Modification Methylases/genetics

KW - DNA Repair Enzymes/genetics

KW - Humans

KW - Promoter Regions, Genetic/genetics

KW - Retrospective Studies

KW - Sequence Analysis, DNA

KW - Survival Analysis

KW - Triple Negative Breast Neoplasms/genetics

KW - Tumor Suppressor Proteins/genetics

U2 - 10.1371/journal.pone.0238021

DO - 10.1371/journal.pone.0238021

M3 - SCORING: Journal article

C2 - 32841306

VL - 15

SP - e0238021

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 8

ER -