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| Status |
Public on Sep 27, 2023 |
| Title |
Integrated chromatin accessibility and gene expression landscape of human triple-negative breast cancer cell lines reveals variation by patient donor ancestry [Bulk ATAC-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
African American (AA) women are at increased risk of developing and dying from Triple-Negative Breast Cancer (TNBC), an aggressive breast cancer subtype, compared to European American (EA) women in the United States. In addition to social determinants, further investigation into biologic factors that contribute to these disparities is needed to fully understand this multi-factorial problem. In particular, the epigenetics of racial/population diversity and its influence on breast cancer incidence and outcomes remains underexplored. Using ATAC-sequencing and RNA-sequencing, we characterized differences in chromatin accessibility and gene expression between EA-derived versus AA-derived TNBC cell lines (N=9). Our analyses revealed significant differences in transcription factor binding and downstream gene expression associated with cancer stemness, resistance, and epithelial to mesenchymal transition. Differences were exacerbated under conditions of hypoxia. Together, these data suggest a differential chromatin and transcriptomic landscape that may contribute to worsened TNBC biology in women of African ancestry. Additionally, as many of these cell lines are used routinely in biomedical research, these findings also indicate that the ancestral origin of patient derived cell lines matters and may contribute to biologic variation in experimental data, suggesting that inclusion of diversely sourced cell lines should be considered in experimental design.
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| Overall design |
Cell revival, cell lysis, transposition, and DNA extraction were done using a published method by Corces et al., 2017 (PMID: 28846090) with some modifications for cryopreserved cell processing (Caravaca et al., 2022). The peaks (open chromatin regions) of the above breast cancel cell lines were generated by sequencing using Illumina NextSeq 2000 P2.
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| Contributor(s) |
Harris AR, Panigrahi G, Liu H, Koparde V, Bailey-Whyte M, Dorsey TH, Yates C, Ambs S |
| Citation(s) |
37732899 |
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| Submission date |
Jan 18, 2023 |
| Last update date |
Oct 19, 2023 |
| Contact name |
Stefan Ambs |
| E-mail(s) |
ambss@mail.nih.gov
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| Phone |
240-760-6836
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| Organization name |
NCI
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| Department |
CCR
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| Lab |
LHC
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| Street address |
Building 37, Room 3050B
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892-4258 |
| Country |
USA |
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| Platforms (1) |
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| Samples (50)
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| This SubSeries is part of SuperSeries: |
| GSE223183 |
Integrated chromatin accessibility and gene expression landscape of human triple-negative breast cancer cell lines reveals variation by patient donor ancestry |
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| Relations |
| BioProject |
PRJNA925199 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE223182_ccbr1005_project1_chromVAR.tnbc_only.results.xlsx |
142.1 Kb |
(ftp)(http) |
XLSX |
| GSE223182_ccbr1181_ChromVAR_results.xlsx |
507.4 Kb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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