Abstract A08: Epigenetic heterogeneity in triple-negative breast cancer

Abstract

Abstract Triple-negative breast cancer (TNBC) is defined by the absence of estrogen/progesterone receptor (ER/PgR) expression and HER2 amplification. Patients with TNBC have a higher rate of distant recurrence and a poorer prognosis than women with other breast cancer subtypes, since targeted therapy is not available for them. TNBC is a highly heterogeneous group of tumors and the underlying biology of these tumors should be substantially different. Stratification is essential for selection of appropriate therapy. We have previously identified key regulators that define basal-like (ER-/PgR-/HER2-) and luminal (ER+/PgR+ and/or HER2+) breast cancer cell phenotypes by using combined somatic cell genetic and integrative epigenomic approaches (Su et al., Cell Reports 2015). We found that common core epigenetic programs in luminal tumors are defined by FOXA1 super-enhancers; however, apart from displaying extinguished luminal features, the basal-like phenotype is not defined by a specific epigenetic state and displays a high degree of heterogeneity. In this study, we aimed to identify a key regulator that can classify TNBCs into two groups, so that it could help improve our understanding of biology and explain the epigenetic heterogeneity in TNBC. We first reanalyzed our original multi-omics data of hetero-fusion cells in the previous study and also performed an integrated analysis of genomic, transcriptomic, and epigenomic data obtained from the TCGA project. We finally focused on a transcription factor (TF-X), whose function is currently unknown. TF-X is upregulated in a subset of TNBCs and the expression level of the gene is associated with poor prognosis in TNBC. Knockdown of TF-X decreased cell survival rate and changed cellular morphology of the cells. We are currently doing further functional analysis of TF-X. Our findings seem to imply that TF-X is one of the key regulators that govern cellular property of TNBC. Note: This abstract was not presented at the conference. Citation Format: Reo Maruyama, Liying Yang, Kohei Kumegawa. Epigenetic heterogeneity in triple-negative breast cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr A08.