Abstract P2-04-06: Changes of DNA methylation in the development of breast cancer

Abstract

Abstract Aberrant DNA methylation plays an important role in breast cancer initiation and progression via inactivation of tumor suppressor genes and activation of oncogenes. To better understand the changes of DNA methylation in the development of breast cancer, we analyzed genome-wide DNA methylation DNA data in breast tumor, adjacent normal tissue, and normal breast tissue from healthy women. Using the IIILumina MethylationEPIC array, we investigated approximately 850,000 CpG sites. After quality control, 747,803 probes were retained and included the further analysis. To identify DNA methylation markers associated with breast cancer, we performed differential methylation analysis using ChAMP package implemented in Bioconductor. We identified 590 CpG sites that were differentially methylated (P<1X10-4) between tumor and normal, and 637 between tumor and adjacent normal tissue samples. Further pathway analyses revealed that changes in DNA methylation between tumor and normal breast tissue were mainly involved in neurogenesis and neuro differentiation, oxidative stress, insulin secretion and epithelial morphogenesis; while changes in DNA methylation between tumor and adjacent normal tissue were mainly involved in angiogenesis, cell morphogenesis, and cell component movement. We further validated our findings using RNA-seq data. Our results suggested distinct DNA methylation changes involved in different biological pathways, reflecting potential causal and reactive biological mechanisms in the initiation and the progression of breast cancer. Citation Format: He C, Lin N, Shendre A, Jiang G, Lin H, Wan J, Liu Y. Changes of DNA methylation in the development of breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-04-06.