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en O6-Methylguanine-DNA Methyltransferase and ATP-Binding Cassette Membrane Transporter G2 Promotor Methylation: Can Predict the Response to Chemotherapy in Advanced Breast Cancer? زیست شناسی ملکولی Molecular Biology مقالات اصلی Original Article Background: ATP-binding cassette membrane transporter G2 (ABCG2) gene is one of transporter family and well characterized for their association with chemoresistance. Promoter methylation is a mechanism for regulation of gene expression. O6-Methyl guanine DNA methyl transferase (MGMT) gene plays a fundamental role in DNA repair. MGMT has the ability to remove alkyl adducts from DNA at the O6 position of guanine. Alkylating agents exert their function through adding these alkyls adducts to DNA leading to cell death unless it is repaired by MGMT. MGMT promoter was found to be methylated in several malignancies. The aim of the present work is to study the relation of MGMT and ABCG2 promoter methylation status in advanced breast cancer patients to response to cyclophosphamide–doxorubicin (AC) based therapeutic regime. Methods: This retrospective study included Forty-two female patients with advanced breast cancer assessed before receiving chemotherapy and after the completion of regimens. They were grouped into responders and non-responders according to RECIST criteria. Methylation analysis of MGMT and ABCG2 genes were performed on breast cancer tissues. Results: MGMT promoter was methylated in 40.5% of the cases. ABCG2 promoter was methylated in 14.3% of cases. There was no statistically significant association between MGMT and ABCG2 promoter methylation status and clinicopathological parameters. There was statistically significant association between methylation status of both promoters and response to AC when followed by Taxane. Conclusions: Methylation of MGMT and ABCG2 promoters combined could be a potential predictive factor for response to cyclophosphamide-doxorubicin based therapeutic regime. ABCG2, Breast cancer, Chemoresistance, DNA methylation, MGMT. 20 29 http://rbmb.net/browse.php?a_code=A-10-847-1&slc_lang=en&sid=1 Sara Ahmed Aglan 100319475328460012312 100319475328460012312 No Department of Chemical Pathology, Medical Research Institute, Alexandria University, Alexandria, Egypt. Ahmad Mohamad Zaki 100319475328460012313 100319475328460012313 No Department of Chemical Pathology, Medical Research Institute, Alexandria University, Alexandria, Egypt. Amel Sobhy El Sedfy 100319475328460012314 100319475328460012314 No Department of Pathology, Medical Research Institute, Alexandria University, Alexandria, Egypt. Heba Gaber El-Sheredy heba.gaber99@yahoo.com. 100319475328460012315 100319475328460012315 Yes Department of Cancer Management and Research, Medical Research Institute, Alexandria University, Alexandria, Egypt. Ola Hussein Elgaddar 100319475328460012316 100319475328460012316 No Department of Chemical Pathology, Medical Research Institute, Alexandria University, Alexandria, Egypt.