Abstract A04: Differential DNA methylation and network analysis in African American breast cancer

Abstract

Abstract African Americans (AAs) have more severe breast cancer, and higher death rate from breast cancer, than that of Caucasian Americans (CAs) even after socioeconomic status are accounted for. Various studies have been done to understand the biological mechanism of this health disparity. In this study, we performed a genome-wide differential DNA methylation analysis between AA and CA breast cancer patients. We analyzed differentially methylated positions (DMPs) and differentially methylated regions (DMRs) using data from 143 AA and 554 CA breast tumor tissues available at the Cancer Genome Atlas (TCGA). We found that there were 1232 DMPs and 661 DMRs between AA and CA breast cancer patients. Both DMP and DMR showed that PACS2 and ATP1A4 were highly differentially methylated among other genes. Network analysis showed that differential methylation occurred significantly in p53, EGFR, and ERS1 subnetwork, which is consistent from an early study on differentially expressed transcripts. We also conducted a correlation analysis between gene expression by RNA sequencing and DNA methylation, which showed that expressions of 129 genes with either DMP or DMR were highly negatively correlated with the corresponding DNA methylations, suggesting that these DNA methylation may play important roles in the breast cancer health disparity observed in AA women. Our discoveries may help researchers to better understand the biological factors for breast cancer health disparity and the biology of breast cancer in general. The genes or DMPs/DMRs identified may serve as the starting points for further experimental validations towards discovering biomarkers for cancer diagnosis and prognosis, and drug targets for personalized treatments. Citation Format: Kaixian Yu, Albert Steppi, Yun Xu, Ke Tang, Jinfeng Zhang. Differential DNA methylation and network analysis in African American breast cancer. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr A04.