Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA222876 | ENA |
REPOSITORIES: ENA
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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.
2013-01-29 | GSE26232 | GEO
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.
2013-01-29 | GSE26214 | GEO
Project description:Analysis of the levels of circulating miRNAs from women with early stage breast cancer and matched healthy controls. miRNAs in plasma samples from 20 women with early stage breast cancer (10 Caucasian American and 10 African American) compared with 20 matched healthy controls (10 Caucasian American and 10 African American).
2011-01-16 | E-GEOD-22981 | biostudies-arrayexpress
Project description:CIDR_Epidemiology of Breast Cancer Subtypes in African American Women
| PRJNA222875 | ENA
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
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
Project description:African American Breast Cancer Consortium (AABC) Study
| PRJNA271632 | ENA
Project description:Background: Obesity is a risk factor for breast cancer in postmenopausal women and is associated with decreased survival and less favorable clinical characteristics such as greater tumor burden, higher grade, and poor prognosis, regardless of menopausal status. Despite the negative impact of obesity on clinical outcome, molecular mechanisms through which excess adiposity influences breast cancer etiology are not well-defined. Methods: Affymetrix U133 2.0 gene expression data were generated for 405 primary breast tumors using RNA isolated from laser microdissected tissues. Patients were classified as normal-weight (BMI<25), overweight (BMI 25-29.9) or obese (BMI>30). Statistical analysis was performed by ANOVA using Partek Genomics Suite version 6.6 using a false discovery rate <0.05 to define significance. Results: Obese patients were significantly more likely to be diagnosed >50 years or with African American ancestry compared to lean or overweight women. Pathological characteristics, including tumor stage, size or grade, lymph node status, intrinsic subtype, and breast cancer mortality did not differ significantly between groups. No significant gene expression differences were detected by BMI In a non-stratified analysis which included all subtypes or within luminal B, HER2-enriched or basal-like subtypes. Within luminal A tumors, however, 84 probes representing 77 genes from pathways such as cell cycle, p53 and mTOR signaling, tight junctions and a number of cancer associated pathways were differentially expressed. Conclusions: Identification of transcriptome differences in luminal A tumors from normal-weight compared to obese women suggests that obesity alters gene expression within ER+ tumor epithelial cells. Alterations of pathways involved in cell cycle control, tumorigenesis and metabolism may promote cellular proliferation and provide a molecular explanation for less favorable outcome of obese women with breast cancer. Targeted treatments, such as mTOR inhibitors, may allow for improved treatment and survival of obese women, especially African American women, who are more likely to be obese and suffer outcome disparities.
2016-03-08 | GSE78958 | GEO
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
Project description:Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with no targeted therapeutics. The luminal androgen receptor (LAR), one of the six TNBC subtypes, constitutes 15% of TNBC and is enriched for AR and AR-target genes. Here, we show that a cohort of TNBC not only expresses full-length AR (AR-FL) at a much higher rate (~80%) than previously reported, but also expresses AR splice variants (AR-SVs) (~20%), subclassifying the LAR-TNBC subtype into LAR-FL, LAR-AR-SV, or dual positive. Higher AR and AR-SV expression and corresponding aggressive phenotypes were observed predominantly in specimens obtained from African American women. RNA sequencing of LAR TNBC specimens indicates an enrichment of hallmark interferon, JAK-STAT, and androgen signaling pathways, which were exclusive to AR-expressing epithelial cancer cells as demonstrated by spatial genomics. LAR and LAR-AR-SV TNBC cell proliferation, orthotopic cell line and patient-derived xenograft, and patient-derived tumor explants growth were inhibited by AR N-terminal domain (NTD)-binding selective AR degrader (SARD) that irreversibly inhibits AR or by the JAK inhibitor ruxolitinib. Subsequent biochemical analysis suggests that STAT1 is an AR coactivator, and SARD or ruxolitinib blocks this coactivation. Collectively, our work identifies and characterizes a pharmacologically targetable and previously unreported TNBC subtype predominantly in African American women and identifies a growth-promoting interaction between AR and JAK-STAT signaling.
2023-10-04 | GSE244282 | GEO