Comparative Characterization of 3D Chromatin Organization in Triple-Negative Breast Cancers [RNA-seq]

Triple-negative breast cancer (TNBC) is malignant cancer with a high risk of recurrence. To date, the underlying 3D chromatin organizations of TNBC have remained unclear. Here, using in situ Hi-C, we characterized the 3D chromatin organizations in cells representing five distinct subtypes of breast cancer (including TNBC) and TNBC tissues, compared to normal cells/tissues. We found that the global and local 3D architectures are severely disrupted in TNBC cells. Importantly, we detected CTCF-dependent TNBC-susceptible loss/gain of 3D chromatin organizations and found that these changes were strongly associated with perturbed chromatin accessibility and transcriptional dysregulations. Although some discrepancies exist between TNBC cell lines and tissues, we observed that perturbed local 3D architectures found in TNBC cells are partially conserved in TNBC tissues. Furthermore, we discovered distinct tissue-specific chromatin loops by comparing normal and TNBC tissues. Collectively, our findings provide important features of 3D chromatin organization in TNBC. For RNA-seq experiment (cell lines) : Strand-specific mRNA-seq of Human mammary epithelial cell (HMEC, as a control) and the cell line of 5 breast cancer subtypes, The cell lines were performed the biological replicates. For RNA-seq experiment (Tissues) : Strand-specific mRNA-seq of Five Contralateral breast normal tissue, fourteen triple negative breast cancer (IDC) tissues.