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Characterization of a Castrate Resistant Prostate Cancer Xenograft Derived from a Patient of West African Ancestry

ABSTRACT: Characterization of a Castrate Resistant Prostate Cancer Xenograft Derived from a Patient of West African Ancestry

PROVIDER: PRJNA610513 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11243100_1.fastq.gz	Fastqsanger.gz
	SRR11243100_2.fastq.gz	Fastqsanger.gz
	SRR11243101_1.fastq.gz	Fastqsanger.gz
	SRR11243101_2.fastq.gz	Fastqsanger.gz
	SRR11243102_1.fastq.gz	Fastqsanger.gz

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Characterization of a Castrate Resistant Prostate Cancer Xenograft Derived from a Patient of West African Ancestry

Project description:Here we report the establishment and characterization of a Prostate Cancer Patient Derived Explant (PCPDX) from a patient of West African ancestry with metastatic castration resistant disease. The following data represents gene expression in a series of mice carrying this PCPDX and undergoing different treatment courses. Mice were treated for 10 weeks with either Enzalutamide, Cisplatin, or Docetaxel, or appropriate vehicle controls.

2020-08-01 | GSE146402 | GEO

RNA splicing and aggregate gene expression differences between lung squamous cell carcinoma from patients of West African and European ancestry

Project description:Study of genes that are differentially spliced and differentially expressed between African Americans and whites with lung squamous cell cancer. Despite racial disparities in lung cancer, the molecular landscape of lung cancer in patients of African ancestry remains underexplored. Population-related differences in alternative RNA splicing have not been explored. We identified differentially spliced genes and differentially expressed genes between lung squamous cell carcinoma from patients of West African and European ancestry.

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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.

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Homo sapiens strain:(ASW) African ancestry in South West US

Project description:Exome sequencing of (ASW) African ancestry in South West US population

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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.

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Characterization of a castrate-resistant prostate cancer xenograft derived from a patient of West African ancestry.

Project description:BackgroundProstate cancer is a clinically and molecularly heterogeneous disease, with highest incidence and mortality among men of African ancestry. To date, prostate cancer patient-derived xenograft (PCPDX) models to study this disease have been difficult to establish because of limited specimen availability and poor uptake rates in immunodeficient mice. Ancestrally diverse PCPDXs are even more rare, and only six PCPDXs from self-identified African American patients from one institution were recently made available.MethodsIn the present study, we established a PCPDX from prostate cancer tissue from a patient of estimated 90% West African ancestry with metastatic castration resistant disease, and characterized this model's pathology, karyotype, hotspot mutations, copy number, gene fusions, gene expression, growth rate in normal and castrated mice, therapeutic response, and experimental metastasis.ResultsThis PCPDX has a mutation in TP53 and loss of PTEN and RB1. We have documented a 100% take rate in mice after thawing the PCPDX tumor from frozen stock. The PCPDX is castrate- and docetaxel-resistant and cisplatin-sensitive, and has gene expression patterns associated with such drug responses. After tail vein injection, the PCPDX tumor cells can colonize the lungs of mice.ConclusionThis PCPDX, along with others that are established and characterized, will be useful pre-clinically for studying the heterogeneity of prostate cancer biology and testing new therapeutics in models expected to be reflective of the clinical setting.

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Uncovering the role admixture in health disparities: Association of hepatocyte gene expression and DNA methylation to African Ancestry in African-Americans [Methylation]

Project description:In African Americans (AA), the proportion of West African ancestry (WAA) may explain the genetic drivers of health disparities in disease. Analysis of RNA sequencing data from sixty AA-derived primary hepatocytes identified 32 gene expression profiles associated with WAA (FDR <0.05) with enrichment in angiogenesis and inflammatory pathways (FDR <0.1). Association of DNA methylation to WAA identified 1037 differentially methylated regions (FDR <0.05), with hypomethylated genes enriched for drug response pathways. Within the PharmGKB pharmacogene, VDR, PTGIS, ALDH1A1, CYP2C19 and P2RY1 were associated with WAA (p <0.05) with replication of CYP2C19 and VDR in the GTEx liver cohort. For every 1% increment in WAA, P2RY1 gene expression increased by 1.6% and CYP2C19 gene expression decreased by 1.4%, suggesting effects on clopidogrel response and platelet aggregation. We conclude that WAA contributes to variablity in hepatic gene expression and DNA methylation with identified genes indicative of health disparities prevalent in AAs.

2019-10-31 | GSE123995 | GEO

Uncovering the role admixture in health disparities: Association of hepatocyte gene expression and DNA methylation to African Ancestry in African-Americans [RNA-seq]

2019-10-31 | GSE124074 | GEO

Uncovering the role admixture in health disparities: Association of hepatocyte gene expression and DNA methylation to African Ancestry in African-Americans [RNA-seq]

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A single-cell atlas of West African lungfish respiratory system reveals evolutionary adaptations to terrestrialization

Project description:The six species of lungfish possess both lungs and gills and are the closest extant relatives of tetrapods. Here, we report a single-cell transcriptome atlas of the West African lungfish (Protopterus annectens). This species manifests the most extreme form of terrestrialization, a life history strategy to survive dry periods in five lungfish species that can last for years, characterized by dormancy and reversible adaptive changes of the gills and lungs. Our atlas highlights the cell type diversity of the West African lungfish, including gene expression consistent with phenotype changes of terrestrialization. Comparisons with terrestrial tetrapods and ray-finned fishes revealed broad homology between the swim bladder and lung cell types as well as shared and idiosyncratic changes of the external gills of the West African lungfish and the internal gills of Atlantic salmon. The single-cell atlas presented here provides a valuable resource for further exploring the evolution of the vertebrate respiratory system and the diversity of lungfish terrestrialization.

2023-08-05 | GSE240094 | GEO

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