title: DNA methylation of circulating DNA: a marker for monitoring efficacy of neoadjuvant chemotherapy in breast cancer patients.
abstract: Identification of biomarkers for monitoring efficacy of neoadjuvant chemotherapy in breast cancer patients is of utmost importance in individual tailoring of treatment and save from toxicity due to non-effective drugs. We hypothesized that methylation of circulating tumor-specific DNA may reflect changes in tumor burden in response to chemotherapy and help stratify responders from non-responders. The aim of this study was to evaluate the potential of methylation changes in circulating DNA to monitor treatment response of breast cancer patients. Six consecutive sera samples collected from 30 breast cancer patients undergoing neoadjuvant chemotherapy were analyzed for methylation status of a panel of five genes namely, BRCA1, MGMT, GSTP1, Stratifin, and MDR1. Among these five genes, BRCA1 methylation frequency was different among responders and non-responders groups. The correlation coefficients between total gene methylation with initial chemotherapy and tumor volume reduction were R(2) = 0.8 and R(2) = 0.05 in the responders and non-responders groups, respectively. Our findings warrant further development of this approach for monitoring response in patients undergoing neoadjuvant chemotherapy.
authors: Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
authors: Gayatri
authors: G
authors: Sharma
authors: Sameer
authors: S
authors: Mirza
authors: Rajinder
authors: R
authors: Parshad
authors: Siddartha Datta
authors: SD
authors: Gupta
authors: Ranju
authors: R
authors: Ralhan
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000097:blood* / Q000235:genetics; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D005092:Exonucleases / Q000235:genetics; D005095:Exoribonucleases; D005260:Female; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D048948:14-3-3 Proteins; C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D004247:DNA; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human; D045643:DNA Repair Enzymes