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Integrated chromatin accessibility and gene expression landscape of human triple-negative breast cancer cell lines reveals variation by patient donor ancestry [RNA-seq]

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE223181 | GEO | 2023/09/27

REPOSITORIES: GEO

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Integrated chromatin accessibility and gene expression landscape of human triple-negative breast cancer cell lines reveals variation by patient donor ancestry [Bulk ATAC-seq]

Project description: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.

2023-09-27 | GSE223182 | GEO

Genomic profiles vary with race and subtype in young African American and European American breast cancer (SNP)

2013-01-29 | GSE26232 | GEO

Genomic profiles vary with race and subtype in young African American and European American breast cancer (aCGH)

2013-01-29 | GSE26214 | GEO

Genomic profiles vary with race and subtype in young African American and European American breast cancer (SNP)

Project description:In the United States, African-American (AA) women are more likely to develop early-onset breast cancer and have historically poorer outcomes due to this disease compared to European-American (EA) women. Here, we analyzed genomic profiles of breast tumors from young women (<50 years old), matched by tumor subtype, histological grade, and ethnicity (African-American, AA, compared to European-American, EA). DNA copy number alterations (CNAs) were analyzed on the Affymetrix Human SNP Array v 6.0 platform. The study provides insight into the genetic component of ethnicity-related breast cancer health disparities. DNA copy number alterations (CNAs) and genotypes were analyzed using the Affymetrix SNP 6.0 platform. Breast tumor samples from young women (< 50 years old) were matched as follows: a matched pair consists of one AA and one EA sample, matched for tumor grade and tumor subtype (based on immunohistochemical analysis of ER, PR, and HER2 status). DNA from forty-four samples (22 AA, 22 EA) was analyzed on the Affymetrix SNP 6.0 array according to manufacturer’s directions.

2013-01-29 | E-GEOD-26232 | biostudies-arrayexpress

Genomic profiles vary with race and subtype in young African American and European American breast cancer (aCGH)

Project description:In the United States, African-American (AA) women are more likely to develop early-onset breast cancer and have historically poorer outcomes due to this disease compared to European-American (EA) women. Here, we analyzed genomic profiles of breast tumors from young women (<50 years old), matched by tumor subtype, histological grade, and ethnicity (African-American, AA, compared to European-American, EA). DNA copy number alterations (CNAs) were analyzed using a 32K BAC tiling path array. The study provides insight into the genetic component of ethnicity-related breast cancer health disparities. Breast tumor samples from young women (< 50 years old) were matched as follows: a matched pair consists of one AA and one EA sample, matched for tumor grade and tumor subtype (based on immunohistochemical analysis of ER, PR, and HER2 status). 44 experiments; each experiment is tumor DNA versus reference control DNA (AF) isolated from the blood of a 25-year-old African-American female with no familial or personal history of breast cancer. Additional control experiments included the AF reference versus the well-characterized F1 reference, and 3 self-self hybridization controls (AF versus AF).

2013-01-29 | E-GEOD-26214 | biostudies-arrayexpress

Yale Triple Negative Breast Cancer Cohort

2013-08-15 | GSE46581 | GEO

Spatial transcriptomics of triple negative breast cancer

Project description:Triple negative breast cancer (TNBC) is an aggressive and clinically challenging subtype of breast cancer. TNBC disporportionately affects African-American (AA) women, but the biological basis of this disparity is not understood. To gain a better understanding of TNBC, particularly in AA patients, we applied spatial transcriptomics to thoroughly characterize gene expression and tissue architecture in TNBC. Our cohort consisted of 22 patients, 15 of whom were AA, and 7 who were Caucasian. We obtained 2 sections from each patient's tumor (except for patient 19) for a total of 43 samples.

2022-11-02 | GSE210616 | GEO

Molecular Dissection of Disease Heterogeneity in SLE

Project description:Systemic lupus erythematosus (SLE) affects 1 in 537 of African American (AA) women, which is >2-fold more than European American (EA) women. AA patients also develop the disease at a younger age, have more severe symptoms, and a greater chance of early mortality. We used a multi-omics approach to uncover ancestry-specific immune alterations in SLE patients and healthy controls that may contribute to disease disparities. Cell composition, signaling, and epigenetics were evaluated by mass cytometry; droplet-based single cell transcriptomics and paired proteogenomics (scRNA-Seq/scCITE-Seq). Soluble mediator levels were measured in plasma and stimulated whole blood. TLR3/4/7/8/9 gene expression pathways in B cells and monocytes were enhanced in AA SLE patients compared to EA patients. TLR7/8/9 and IFN phospho-signaling responses were also heightened in healthy AA versus EA controls. Exposure of AA and EA healthy control cells to TLR7/8/9 agonists or IFN resulted in altered immune cell compositions that recapitulated the ancestry-associated differences in SLE patients. These data support that ancestry-based differences in TLR7/8, TLR9, and IFN responses that can be detected in healthy individuals could influence lupus disease course and severity.

2023-10-11 | GSE189050 | GEO

Yale Triple Negative Breast Cancer Cohort

Project description:Triple negative breast cancer (TNBC) is characterized by high proliferation, poor differentiation and a poor prognosis due to high rates of recurrence. Despite lower overall incidence African American (AA) patients suffer from higher breast cancer mortality in part due to the higher proportion of TNBC cases among AA patients compared to European Americans (EA). It was recently shown that the clinical heterogeneity of TNBC is reflected by distinct transcriptional programs with distinct drug response profiles in preclinical models. In this study, we used gene expression profiling and immunohistochemistry to eluicidate potential differences between TNBC tumors of EA and AA patients on a molecular level. WG-DASL experiment of 90 FFPE samples of ER, PR and HER2 (triple) negative breast cancer samples diagnosed between 1987 and 2007. Invasive disease was identified on H&E sections by the study pathologist and one to three 1.5 mm cores were punched from the top down in the designated tumor areas of each FFPE block. The cores were deparaffinized with xylene at 50°C for 3 minutes. RNA was extracted using the RecoverAll Total Nucleic Acid Isolation kit (Applied Biosystems) following the manufacturer's protocol. The isolated RNA was hybridized to Whole-Genome DASL (HumanRef8 V 3.0, Illumina) at the Yale Center for Genome Analysis. 90 primary tumor RNA samples from 90 patients were adequate for analysis and passed Quality control.

2013-08-15 | E-GEOD-46581 | biostudies-arrayexpress

MicroRNA expression profiling of the prostate biopsy samples from African American and European American prostate cancer patients

Project description:Prostate cancer (PCa) tends to be more aggressive and lethal in African Americans (AA) compared to European Americans (EA). To further understand the thebiological risk factors associated with PCa disparities observed in AA and EA patients, we performed microRNA profiling using Agilent Human miRNA arrays to identify the differentially expressed microRNAs beween: 1) AA and EA PCa patients; 2) AA PCa vs. AA normal; and 3) EA PCa vs. EA normal. 54 prostate biopsy specimens (tumor and adjacent normal tissues) were collected from 14 African American and 13 European American prostate cancer patients. 54 RNA samples, purified from the collected biopy specimens using Qiagen miRNeasy kit, were process and applied to Agilent human miRNA arrays. Array data was normalized and analyzed using Agilent GeneSpring program.

2015-07-27 | E-GEOD-64318 | biostudies-arrayexpress

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