Abstract
Abstract Epigenetic alterations are common in breast cancer, yet how these modifications contribute to chemotherapy response is poorly understood. This study aimed to define a DNA methylation profile associated with response to neo-adjuvant treatment in breast cancer and to identify possible candidate genes associated with resistance as predictors. Eleven pre-treatment and 12 post-treatment serum samples with 6 pairs of FFPE tissues were collected in neo-adjuvant chemotherapy with operable and locally advanced breast cancer. Illumina HumanMethylation450K BeadChip technology for serum DNA and Roche Nimblegen Human DNA Methylation 3x720K CpG Island Plus RefSeq Promoter Arrays, MeDIP-chip technology for FFPE DNA were used for simultaneous analysis of 450,000 CpG sites for serum DNA and 27,728 for FFPE DNA, respectively. Genes generated from pre-treatment samples were compared with those genes obtained from post-treatment samples, which showed differential modulation following neo-adjuvant chemotherapy. Association on 11 pre-treatment serum DNA highlighted 102 genes significantly related to Ki67 level change as the treatment response (p =0.2) after excluding genes changed by neo-adjuvant chemotherapy. Among them, 16 genes showed consistent methylation levels between serum and tissue (hypermethylation including ITIH3, p-value=0.0015, 8.9 fold-change; hypomethylation including ARID3A, p-value=0.0037, 1.4 fold-change). Hypomethylation of DBH, PRDM16, SLC12A7 and VSX2 in pre-treatment serum and tissue DNA were also predicted to another response surrogate measured by the changes of tumor size (p =0.2). Our study suggests that testing for methylation levels of genes identified in this study may be beneficial in predicting individual patient response to neo-adjuvant therapies. Citation Format: Ji-Yeob Choi, Taehyun Kim. Association between DNA methylation profile and neo-adjuvant treatment response in breast cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1181. doi:10.1158/1538-7445.AM2013-1181
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