Affymetrix Oncoscan array data for aggressive variant prostate cancer (AVPC) samples
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE73902 | GEO | 2015/10/10
SECONDARY ACCESSION(S): PRJNA298365
REPOSITORIES: GEO
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Project description:Aggressive cancers and normal stem cells often share similar molecular and functional traits. It is unclear if aggressive phenotypes of prostate cancer molecularly resemble normal stem cells residing within the human prostate. We performed high-throughput RNA sequencing on uncultured, highly purified epithelial populations from human prostates obtained after radical prostatectomy. We found the basal population to be defined by genes associated with developmental programs, epigenetic remodeling, and invasiveness. We further generated a 91-gene basal signature and applied it to gene expression datasets from patients with organ-confined or castration-resistant, metastatic prostate cancer. Metastatic prostate cancer was more enriched for the basal stem cell signature than organ-confined prostate cancer. Moreover, histological subtypes within prostate cancer metastases varied in their enrichment of the stem cell signature with small cell neuroendocrine carcinoma being the most stem cell-like. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common to all three signatures. These results suggest that the most aggressive variants of prostate cancer share a core transcriptional program with normal prostate basal stem cells. Transcriptional analysis of 10 uncultured prostatic basal and luminal populations from either the benign or malignant prostate tissue of 8 human prostate cancer patients by high-throughput RNA-seq
2016-06-01 | E-GEOD-82071 | biostudies-arrayexpress
Project description:Aggressive cancers and normal stem cells often share similar molecular and functional traits. It is unclear if aggressive phenotypes of prostate cancer molecularly resemble normal stem cells residing within the human prostate. We performed high-throughput RNA sequencing on uncultured, highly purified epithelial populations from human prostates obtained after radical prostatectomy. We found the basal population to be defined by genes associated with developmental programs, epigenetic remodeling, and invasiveness. We further generated a 91-gene basal signature and applied it to gene expression datasets from patients with organ-confined or castration-resistant, metastatic prostate cancer. Metastatic prostate cancer was more enriched for the basal stem cell signature than organ-confined prostate cancer. Moreover, histological subtypes within prostate cancer metastases varied in their enrichment of the stem cell signature with small cell neuroendocrine carcinoma being the most stem cell-like. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common to all three signatures. These results suggest that the most aggressive variants of prostate cancer share a core transcriptional program with normal prostate basal stem cells.
2016-06-01 | GSE82071 | GEO
Project description:Purpose: Small-cell prostate carcinoma (SCPC) morphology predicts for a distinct clinical behavior, resistance to androgen ablation, and frequent but short responses to chemotherapy. The model systems we report reflect the biology of the human disease and can be used to improve our understanding of SCPC and to develop new therapeutic strategies for it. Experimental Design: We developed a set of CRPC xenografts and examined their fidelity to their human tumors of origin. We compared the expression and genomic profiles of SCPC and large cell neuroendocrine carcinoma (LCNEC) xenografts to those of typical prostate adenocarcinoma xenografts and used a panel of 60 human tumors to validate our findings using immunohistochemistry. Results: We show that SCPC and LCNEC xenograft models retain high fidelity to their human tumors of origin and are characterized by a marked upregulation of UBE2C and other M-phase cell cycle genes in the absence of AR, retinoblastoma (RB1) and cyclin D1 (CCND1) expression and confirm these findings in a panel of CRPC patients’ samples. In addition, array comparative genomic hybridization of the xenografts showed that the SCPC/LCNEC tumors display more copy number variations than the adenocarcinoma counterparts and that there is amplification of the UBE2C locus and microdeletions of RB1 in a subset of these, but no AR nor CCND1 deletions. Moreover, the AR, RB1, and CCND1 promoters showed no CpG methylation in the SCPC xenografts. Conclusion: Modeling human prostate cancer with xenografts allows in-depth and detailed studies of its underlying biology. The detailed clinical annotation of the donor tumors enables associations of anticipated relevance to be made. Futures studies in the xenografts will address the functional significance of the findings. 22 samples were analysed, that included MDA PCa 79 (n = 3), 117-9 (n = 3), 130 (n = 2), 144-4 (n = 4), 144-13 (n = 5), 146-10 (n = 3), 155-2 (n = 1), and 155-12 (n = 1). MDA PCA 79, 117-9 and 130 samples had the pathologic characteristics of prostate adenocarcinoma and were compared against MDA PCA 144-4, 144-13, 146-10 and 155-12 that have the pathologic features of prostate small cell/ large cell neuroendocrine carcinoma
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2012-01-01 | GSE32967 | GEO
Project description:Purpose: Small-cell prostate carcinoma (SCPC) morphology predicts for a distinct clinical behavior, resistance to androgen ablation, and frequent but short responses to chemotherapy. The model systems we report reflect the biology of the human disease and can be used to improve our understanding of SCPC and to develop new therapeutic strategies for it. Experimental Design: We developed a set of CRPC xenografts and examined their fidelity to their human tumors of origin. We compared the expression and genomic profiles of SCPC and large cell neuroendocrine carcinoma (LCNEC) xenografts to those of typical prostate adenocarcinoma xenografts and used a panel of 60 human tumors to validate our findings using immunohistochemistry. Results: We show that SCPC and LCNEC xenograft models retain high fidelity to their human tumors of origin and are characterized by a marked upregulation of UBE2C and other M-phase cell cycle genes in the absence of AR, retinoblastoma (RB1) and cyclin D1 (CCND1) expression and confirm these findings in a panel of CRPC patients’ samples. In addition, array comparative genomic hybridization of the xenografts showed that the SCPC/LCNEC tumors display more copy number variations than the adenocarcinoma counterparts and that there is amplification of the UBE2C locus and microdeletions of RB1 in a subset of these, but no AR nor CCND1 deletions. Moreover, the AR, RB1, and CCND1 promoters showed no CpG methylation in the SCPC xenografts. Conclusion: Modeling human prostate cancer with xenografts allows in-depth and detailed studies of its underlying biology. The detailed clinical annotation of the donor tumors enables associations of anticipated relevance to be made. Futures studies in the xenografts will address the functional significance of the findings.
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