Chromatin accessibility landscape of human triple-negative breast cancer cell lines reveals variation by patient donor ancestry

Cancer Res Commun. 2023 Sep 21. doi: 10.1158/2767-9764.CRC-23-0236. Online ahead of print.ABSTRACTAfrican American (AA) women have an excessive risk of developing triple-negative breast cancer (TNBC). We employed ATAC-sequencing to characterize differences in chromatin accessibility between 9 commonly used TNBC cell lines derived from patients of European and African ancestry. Principal component and chromosome mapping analyses of accessibility peaks with the most variance revealed separation of chromatin profiles by patient group. Motif enrichment and footprinting analyses of disparate open chromatin regions revealed differences in transcription factor activity, identifying 79 with ancestry-associated binding patterns (FDR < 0.01). AA TNBC cell lines exhibited increased accessibility for 62 transcription factors associated with epithelial-to-mesenchymal transition, cancer stemness/chemotherapeutic resistance, proliferation, and aberrant p53 regulation, as well as KAISO, which has been previously linked to aggressive tumor characteristics in AA cancer patients. Differential ATAC signal analysis identified 1596 genes located within promoters of differentially open chromatin regions in AA-derived TNBC, identifying DNA methyltransferase 1 as the top upregulated gene associated with African ancestry. Pathway analyses with these genes revealed enrichment in several pathways, including hypoxia. Culturing cells under hypoxia showed ancestry-specific stress responses that led to t...
Source: Cell Research - Category: Cytology Authors: Source Type: research