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Ena-DATASET-SLC-12-12-2016-15:06:53:921-242 - samples

ABSTRACT: Whole genome sequencing data of 15 French Caucasian and 10 African-Caribbean men with prostate Cancer.

PROVIDER: EGAD00001003115 | EGA |

REPOSITORIES: EGA

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ena-DATASET-SLC-27-04-2017-10:31:45:151-66 - samples

Project description:Exome sequencing data of 15 French Caucasian and 10 African-Caribbean men with prostate Cancer.

| EGAD00001003306 | EGA

The aim of this project is to identify, on 15 French Caucasian and 10 African-Caribbean men, through an integrative approach of DNA sequencing and transciptomic analyses, relevant genomic events that characterize or allow targeting the various phenotypes of aggressiveness of early stages of prostate cancer.

Project description:Every year about 70,000 new cases of prostate cancer are diagnosed in France and 8,700 men died from this disease. But the incidence and the rate of mortality per 100,000 men in the French West Indies are respectively 1.5x and 2x upper than the rates observed in the metropolitan France. The aim of this project is to identify, on 15 French Caucasian and 10 African-Caribbean men, through an integrative approach of DNA sequencing and transciptomic analyses, relevant genomic events that characterize or allow targeting the various phenotypes of aggressiveness of early stages of prostate cancer.

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Genomic profiling of prostate cancer in African-American patients

Project description:African-Americans with prostate cancer tend to have a more aggressive form of the disease, as compared to their Caucasian counterparts. Nevertheless, African-Americans tend to be underrepresented in most molecular profiling studies of prostate cancer. To investigate DNA copy number alterations (CNAs) in prostate cancer from a cohort of African-Americans, we profiled 20 tumors (each with paired normal) for 500,000 SNPs. Keywords: tumor-normal comparison

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The prostate cancer androgen receptor cistrome in African American men differs from White men and associates with upregulation of lipid metabolism [EA]

Project description:We use androgen receptor chromatin immunoprecipitation (AR ChIP) on frozen prostate adenocarcinoma samples and normal prostate counterparts in men of European ancestry as well as men of African (AA) ancestry and derive a model whereby increased androgen signaling drives higher levels of lipogenesis in AA prostate tumors.

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The prostate cancer androgen receptor cistrome in African American men differs from White men and associates with upregulation of lipid metabolism [AA]

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1,25-Dihydroxyvitamin D3 Suppresses Prognostic Survival Biomarkers Associated with Cell Cycle and Actin Organization in a Non-Malignant African American Prostate Cell Line

Project description:Vitamin D3 is a steroid hormone that has been shown to prevent tumor growth in prostate cells. Not having enough vitamin D3 in the blood has been linked to advanced prostate cancer and mortality, especially in African American men. We wanted to understand how vitamin D affected pathways that keep prostate cells from becoming cancerous, which could lead to new therapeutic targets and treatments, especially for African American men who tend to be more prone to being vitamin D deficient compared to European men. Here, we studied a non-cancerous African American prostate cell line treated with the active form of vitamin D with a concentration similar to what is found in the body for 24 h. Using RNA whole-transcriptome sequencing, we compared these treated cells with untreated cells to assess genes and pathways significantly changed due to treatment. We found that vitamin D affected the activity of 1600 genes, mainly suppressing pathways linked to prostate cell movement, growth, and viability. Only two genes, ANLN and ECT2, were strongly correlated with prostate cancer prognosis. Downregulation of ANLN and ECT2 was also shown to repress signaling pathways involved in prostate cell movement, growth, malignant transformation, and viability. In further validation utilizing prostate cancer cohorts comprised of African American and European American men, patients tended to have better sur-vival rates when these genes were less active. Our results suggest that vitamin D decreases the activity of these genes and could be important for preventing prostate cancer, especially for African American men. This could lead to the development of new treatments targeting specific genes and pathways involved in prostate cancer growth.

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Expression data from prostate cancer epithelial cells from African American and European American men

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ANDROGEN RECEPTOR WITH SHORT POLYGLUTAMINE TRACT PREFERABLY ENHANCES WNT/BETA-CATENIN MEDIATED PROSTATE TUMORIGENESIS

Project description:Polyglutamine (polyQ) tract polymorphism within the human androgen receptor (AR) shows population heterogeneity. African American men possess short polyQ tracts significantly more frequently than Caucasian American men. The length of polyQ tracts is inversely correlated with the risk of prostate cancer, age of onset, and aggressiveness at diagnosis. Aberrant activation of Wnt signaling also reveals frequently in advanced prostate cancer, and an enrichment of androgen and Wnt signaling activation has been observed in African American patients. Here, we investigated aberrant expression of AR bearing different polyQ tracts and stabilized β-catenin in prostate tumorigenesis using newly generated mouse models. We observed an early onset oncogenic transformation, accelerated tumor cell growth, and aggressive tumor phenotypes in the compound mice bearing short polyQ tract AR and stabilized β-catenin. RNA sequencing analysis showed a robust enrichment of Myc-regulated downstream genes in tumor samples bearing short polyQ AR versus those with longer polyQ tract AR. Upstream regulator analysis further identified Myc as the top candidate of transcriptional regulators in tumor cells from the above mouse samples with short polyQ tract AR and β-catenin. Chromatin immunoprecipitation analyses revealed increased recruitment of b-catenin and AR on the c-Myc gene regulatory locus in the tumor tissues expressing stabilized b-catenin and shorter polyQ tract AR. These data demonstrate a promotional role of aberrant activation of Wnt/b-catenin in combination with short polyQ AR expression in prostate tumorigenesis and provide mechanistic insight into aggressive prostatic tumor development that is frequently observed in African American patients.

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Comparative Analysis of 1,152 African-American and European-American Men with Prostate Cancer Identifies Distinct Genomic and Immunological Differences

Project description:Gene expression characteristics of primary prostate cancer tumors from African-Americans are substantially different as compared to European-American men

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Transcription profiling of human prostate cancer epithelial cells from African American and European American men

Project description:African-American (AA) men experience increased risk of developing prostate cancers as well as increased mortality following treatment as compared to European-American (EA) men. The aim of our study was to identify biological factors with potential to predispose AA men to prostate tumor progression and metastasis. High-throughput microarrays were used to investigate differences in global gene expression comparing the two groups. Experiment Overall Design: To identify cancer-specific gene expression patterns in AA men, we established primary prostate cancer epithelial cells from 14 AA and 13 EA men. Cells were cultured for RNA extraction and hybridization on Affymetrix microarrays.

2009-08-07 | E-GEOD-17356 | biostudies-arrayexpress

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