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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]

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

PROVIDER: PRJNA925199 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23116221_1.fastq.gz	Fastqsanger.gz
	SRR23116221_2.fastq.gz	Fastqsanger.gz
	SRR23116222_1.fastq.gz	Fastqsanger.gz
	SRR23116222_2.fastq.gz	Fastqsanger.gz
	SRR23116223_1.fastq.gz	Fastqsanger.gz

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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]

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 | GSE223181 | GEO

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

2023-09-27 | GSE223182 | GEO

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

Project description:Integrated chromatin accessibility and gene expression landscape of human triple-negative breast cancer cell lines reveals variation by patient donor ancestry

| PRJNA925196 | ENA

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

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

| PRJNA925294 | ENA

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-09-27 | GSE223183 | GEO

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

Project description:African 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 the identification of a core set of AA-associated transcription factors, which included members of the Kruppel-like factor and Sp subfamilies, as well as KAISO, and identified ZDHHC1, a gene previously implicated in immunity and STING activation, as the top upregulated AA-specific gene under hypoxia. Together, these data reveal a differential chromatin landscape in TNBC associated with donor ancestry. The open chromatin structure of AA TNBC may contribute to a more lethal disease.

| S-EPMC10552704 | biostudies-literature

African Ancestry Associated Gene Expression Profiles in Triple Negative Breast Cancer Underlie Altered Tumor Biology and Clinical Outcome in Women of African Descent

Project description:Women of sub-Saharan African descent have disproportionately higher incidence of Triple Negative Breast Cancer (TNBC), and TNBC-specific mortality. Population comparative studies show racial differences in TNBC biology, including higher prevalence of basal-like and Quadruple-Negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily United States (US) populations. Due to heterogenous genetic admixture, and biological consequences of social determinants, the true association of African ancestry with TNBC biology is unclear. To address this, we conducted RNAseq on an international cohort of AAs, west and east Africans with TNBC. Using comprehensive genetic ancestry estimation in this African-enriched cohort, we found expression of 613 genes associated with African ancestry and 2000+ associated with regional African ancestry. A subset of African-associated genes also showed differences in normal breast tissue. Pathway enrichment and deconvolution of tumor cellular composition revealed tumor-associated immunological profiles are distinct in patients of African descent.

2022-11-09 | GSE211167 | GEO

Peptide Ancestry Informative Markers in Uterine Neoplasms from Women of European, African and Asian Ancestry

Project description:Characterization of ancestry-linked peptide variants in disease-relevant patient tissues represents a foundational step to connect patient ancestry with molecular disease pathogenesis. Nonsynonymous single nucleotide polymorphisms (SNPs) encoding missense substitutions within tryptic peptides exhibiting high allele frequencies in European, African, and East Asian populations, termed peptide ancestry informative markers (pAIMs), were prioritized from 1000 genomes. In silico analysis shows that as few as 20 pAIMs can determine ancestry proportions similarly to >260K SNPs (R2=0.9905). Multiplexed proteomic analysis of >100 human endometrial cancer cell lines and uterine leiomyoma (ULM) tissues combined resulted in the quantitation of 62 pAIMs that correlate with self-described race and genotype-confirmed patient ancestry. Candidates include a D451E substitution in GC vitamin D-binding protein previously associated with altered vitamin D levels in African and European populations. These efforts describe a generalized set of markers for proteoancestry assessment that will further support studies investigating the impact of ancestry on the human proteome and how this relates to the pathogenesis of uterine neoplasms.

2022-02-16 | PXD029323 | Pride

Immunogenomic Diversity of Triple-Negative Breast Cancers in Obese and Non-obese Black and White Women

Project description:Racial disparities in incidence and outcomes of triple-negative breast cancer (TNBC) have been attributed to ancestry, socioeconomic factors and/or obesity. We studied 253 TNBCs from 128 Black and 125 White women. Arms were balanced for age, AJCC stage, histological grade and molecular subtypes, and differed significantly in BMI distribution, obesity, and Area Deprivation Index. We examined survival rates, whole-transcriptome RNASeq and genetic ancestry. In our sample, Black race or obesity were not intrinsically predictive of poor outcomes. TNBC molecular portraits varied with stage and biological aggressiveness, irrespective of race. We identified a novel group of TNBCs with a distinctive luminal-like and stem-cell-like transcriptional profile that were equally distributed among Blacks and Whites. Genetic ancestry was highly admixed. Immune deconvolution showed a higher abundance of several immune cell populations in tumors from Blacks, which may have precision therapeutic significance, warranting further investigation of potential drivers of tumor immunity.

2025-09-18 | GSE268851 | GEO

Transcription profiling of human samples show variation in african americans with genetic ancestry at most expressed genes

Project description:Variation in gene expression is a fundamental aspect of human phenotypic variation. Several studies have analyzed gene expression levels in populations of different continental ancestry, and concluded that there is variation across populations at a fraction of expressed genes. Here we analyze gene expression levels in African American cell lines, which differ from previously analyzed cell lines in that samples from this population have variable proportions of continental ancestry. We show that for most genes examined, gene expression varies with genetic ancestry. Experiment Overall Design: Lymphoblastoid cell lines (LCL) for 60 HapMap CEU, 60 HapMap YRI, and 82 AFA from the Human Variation Panel were obtained from Coriell Cell Repositories. LCLs were grown in culture, total RNA was extracted and hybridized to Affymetrix HG-FOCUS arrays.

2009-01-14 | E-GEOD-10824 | biostudies-arrayexpress

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