Frequent mutation of the FOXA1 untranslated region in prostate cancer
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001003113 | EGA |
REPOSITORIES: EGA
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Project description:Prostate cancer is the second most common cancer in men and affects 1 in 9 men in the United States. Early screening for prostate cancer often involves monitoring levels of prostate-specific antigen (PSA) and performing digital rectal exams. However, a prostate biopsy is always required for definitive cancer diagnosis. The Early Detection Research Network (EDRN) is a consortium within the National Cancer Institute aimed at improving screening approaches and early detection of cancers. As part of this effort, the Weill Cornell EDRN Prostate Cancer has collected and biobanked specimens from men undergoing a prostate biopsy between 2008 and 2017. In this report, we describe blood metabolomics measurements for a subset of this population. The dataset includes detailed clinical and prospective records for 580 patients who underwent prostate biopsy, 287 of which were subsequentially diagnosed with prostate cancer, combined with profiling of 1,482 metabolites from plasma samples collected at the time of biopsy. We expect this dataset to provide a valuable resource for scientists investigating prostate cancer metabolism.
2023-02-24 | ST002498 | MetabolomicsWorkbench
Project description:In this study, comparison of gene expression profiles in benign epithelia from men with prostate cancer to those of men without prostate cancer reveal differences in several genes associated with prostate cancer.
2010-10-18 | GSE24171 | GEO
Project description:Common epithelial cancers are believed to become more aggressive through the accumulation of multiple independent molecular events that lead to the deregulation of cell signaling. However, the discovery that the majority of prostate cancers harbor gene fusions of the 5'-untranslated region of androgen regulated TMPRSS2 promoter with ETS transcription factor family members has brought this paradigm into question1,2. TMPRSS2-ERG gene fusion is the most common molecular sub-type of prostate cancer. Recent work suggests that the TMPRSS2-ERG fusion is associated with a more aggressive clinical phenotype3. In the most advanced castration resistant prostate cancers where the androgen receptor has been inactivated, the TMPRSS2-ERG fusion remains functionally active. Here we show compelling clinical and gene expression data supporting the existence of a TMPRSS2-ERG fusion prostate cancer subclass. Using expression array profiling on 455 primary prostate tumors, we identified an 87 gene expression signature, distinguishing TMPRSS2-ERG fusion prostate cancer as a discrete molecular entity. Computational analysis suggested that this fusion signature was associated with estrogen receptor signaling. Functional studies demonstrated regulation of the TMPRSS2-ERG fusion transcript by estrogenic compounds. These data identify a previously unrecognized mechanism for regulation of the TMPRSS2-ERG, even in the absence of a functional androgen receptor, and thus may have broader implications in the treatment of prostate cancer. Keywords: Prostate cancer, Expression array, Illumina, gene fusion, TMPRSS2, ERG, Signatures, Estrogen Test Cohort: 388 cases from the population based Swedish-Watchful Waiting cohort. The cohort consists of men with localized prostate cancer (clinical stage T1-T2, Mx, N0); Validation cohort: The PhysiciansM-bM-^@M-^Y Health Study (PHS) cohort included 116 US men diagnosed with incidental prostate cancer between 1983 and 2003; 455 cases were annotated for TMPRSS2-ERG fusion. Test Set: GSM208029 ... GSM208392 Validation Set: GSM208404 ... GSM208512
2008-05-27 | E-GEOD-8402 | biostudies-arrayexpress
Project description:In this study, comparison of gene expression profiles in benign epithelia from men with prostate cancer to those of men without prostate cancer reveal differences in several genes associated with prostate cancer. Custom Agilent 44K whole human genome expression oligonucleotide microarrays were used to profile benign epithelium from prostate needle biopsies from 15 men with high grade(Gleason 8-10) prostate cancer and 14 age- and BMI-matched controls. All samples were laser-capture microdissected and total RNA isolated and amplified prior to hybridization against a common reference pool of prostate tumor cell lines
2010-10-18 | E-GEOD-24171 | biostudies-arrayexpress
Project description:Dataset contains targeted sequencing data of 712 plasma cell free DNA samples and 428 white blood cell samples collected from 428 men with metastatic prostate cancer. Target capture was performed using a hydridization-based custom Roche SeqCap EZ Choice kit, designed to capture all exons of 72 prostate cancer driver genes. Cell free DNA was extracted from 10 mL blood samples. Libraries were sequenced using Illumina HiSeq 2500 or Illumina MiSeq instruments to a median coverage of 750x. 62% of samples had ctDNA fraction above 2% of total cfDNA.
Note that "Dataset type" is erroneously listed as "Amplicon sequencing", because "Captured-based targeted sequencing" or "Hybridization-based targeted sequencing" were not available options in EGA at the time of submission.
| EGAD00001004208 | EGA
Project description:Prostate cancer is the second most occurring cancer in men worldwide, and with the advances made with screening for prostate-specific antigen, it has been prone to early diagnosis and over-treatment. To better understand the mechanisms of tumorigenesis and possible treatment responses, we developed a mathematical model of prostate cancer which considers the major signalling pathways known to be deregulated. The model includes pathways such as androgen receptor, MAPK, Wnt, NFkB, PI3K/AKT, MAPK, mTOR, SHH, the cell cycle, the epithelial-mesenchymal transition (EMT), apoptosis and DNA damage pathways. The final model accounts for 133 nodes and 449 edges. We applied a methodology to personalise this Boolean model to molecular data to reflect the heterogeneity and specific response to perturbations of cancer patients, using TCGA and GDSC datasets.
2022-06-22 | MODEL2106070001 | BioModels
Project description:Prostate cancer incidence and related mortality are disproportionately higher in African American (AA) men than European American (EA) men, but the molecular mechanisms contributing to racial disparities are not fully elucidated. To identify molecular factors that can contribute to disease biology in prostate cancer from AA and EA men, we utilized a multi-omics approach to measure and integrate DNA methylation with gene expression changes. We compared and contrasted results from adjacent non-tumor and tumor tissues from AA and EA men. We found that hypermethylated regions are enriched for PRC2 and H3K27me3 pathways and EZH2/SUZ12 cofactors in a race-independent manner. On the other hand, hypomethylated regions in prostate tumors from AA men were enriched for olfactory/ribosomal pathways as well as distinct cofactors such as CTCF and KMT2A. DNA methylation at transcription start sites and 5’-UTR at GATA3, an androgen receptor (AR) coregulator, is associated with decreased gene expression in prostate tumors of AA men. Our analysis also showed an inverse correlation between DNA methylation and RNA expression of AR transcriptional targets, such as TRIM63, in prostate tumors of AA men. Our observations suggest a dysregulation of the AR signaling pathway in prostate cancer from AA men. To determine whether targeting AR results in race-specific gene expression changes, we utilized a prostate-cancer-specific Boolean network. Our simulation revealed that prolonged AR inhibition results in significant dysregulation in TGF-β, IDH1, and cell cycle pathways in prostate cancer of AA men. We expanded our observation of gene expression changes in the Boolean network and investigated RNA-sequencing data to better understand overall transcriptional alterations occurring in prostate tumors from AA and EA men. We found that gene expression changes related to microtubules, a subset of immune-related, and TMPRSS2-fusion pathways were dysregulated in prostate tumors of AA men and corresponded with progression-free survival of AA men. Altogether, the current study dissects complex signaling networks that are clinically actionable in prostate cancer from AA and EA men.
2024-03-27 | GSE262524 | GEO
Project description:Prostate cancer incidence and related mortality are disproportionately higher in African American (AA) men than European American (EA) men, but the molecular mechanisms contributing to racial disparities are not fully elucidated. To identify molecular factors that can contribute to disease biology in prostate cancer from AA and EA men, we utilized a multi-omics approach to measure and integrate DNA methylation with gene expression changes. We compared and contrasted results from adjacent non-tumor and tumor tissues from AA and EA men. We found that hypermethylated regions are enriched for PRC2 and H3K27me3 pathways and EZH2/SUZ12 cofactors in a race-independent manner. On the other hand, hypomethylated regions in prostate tumors from AA men were enriched for olfactory/ribosomal pathways as well as distinct cofactors such as CTCF and KMT2A. DNA methylation at transcription start sites and 5’-UTR at GATA3, an androgen receptor (AR) coregulator, is associated with decreased gene expression in prostate tumors of AA men. Our analysis also showed an inverse correlation between DNA methylation and RNA expression of AR transcriptional targets, such as TRIM63, in prostate tumors of AA men. Our observations suggest a dysregulation of the AR signaling pathway in prostate cancer from AA men. To determine whether targeting AR results in race-specific gene expression changes, we utilized a prostate-cancer-specific Boolean network. Our simulation revealed that prolonged AR inhibition results in significant dysregulation in TGF-β, IDH1, and cell cycle pathways in prostate cancer of AA men. We expanded our observation of gene expression changes in the Boolean network and investigated RNA-sequencing data to better understand overall transcriptional alterations occurring in prostate tumors from AA and EA men. We found that gene expression changes related to microtubules, a subset of immune-related, and TMPRSS2-fusion pathways were dysregulated in prostate tumors of AA men and corresponded with progression-free survival of AA men. Altogether, the current study dissects complex signaling networks that are clinically actionable in prostate cancer from AA and EA men.
2024-03-27 | GSE262522 | GEO
Project description:Prostate cancer incidence and related mortality are disproportionately higher in African American (AA) men than European American (EA) men, but the molecular mechanisms contributing to racial disparities are not fully elucidated. To identify molecular factors that can contribute to disease biology in prostate cancer from AA and EA men, we utilized a multi-omics approach to measure and integrate DNA methylation with gene expression changes. We compared and contrasted results from adjacent non-tumor and tumor tissues from AA and EA men. We found that hypermethylated regions are enriched for PRC2 and H3K27me3 pathways and EZH2/SUZ12 cofactors in a race-independent manner. On the other hand, hypomethylated regions in prostate tumors from AA men were enriched for olfactory/ribosomal pathways as well as distinct cofactors such as CTCF and KMT2A. DNA methylation at transcription start sites and 5’-UTR at GATA3, an androgen receptor (AR) coregulator, is associated with decreased gene expression in prostate tumors of AA men. Our analysis also showed an inverse correlation between DNA methylation and RNA expression of AR transcriptional targets, such as TRIM63, in prostate tumors of AA men. Our observations suggest a dysregulation of the AR signaling pathway in prostate cancer from AA men. To determine whether targeting AR results in race-specific gene expression changes, we utilized a prostate-cancer-specific Boolean network. Our simulation revealed that prolonged AR inhibition results in significant dysregulation in TGF-β, IDH1, and cell cycle pathways in prostate cancer of AA men. We expanded our observation of gene expression changes in the Boolean network and investigated RNA-sequencing data to better understand overall transcriptional alterations occurring in prostate tumors from AA and EA men. We found that gene expression changes related to microtubules, a subset of immune-related, and TMPRSS2-fusion pathways were dysregulated in prostate tumors of AA men and corresponded with progression-free survival of AA men. Altogether, the current study dissects complex signaling networks that are clinically actionable in prostate cancer from AA and EA men.
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