Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA307348 | ENA |
REPOSITORIES: ENA
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Project description:Prostate cancer-associated stroma (CAS) plays an active role in malignant transformation, tumor progression, and metastasis. Molecular analyses of CAS have demonstrated significant changes in gene expression; however, conflicting evidence exists on whether genomic alterations in benign cells comprising the tumor microenvironment (TME) underlie gene expression changes and oncogenic phenotypes. This study evaluates the nuclear and mitochondrial DNA integrity of prostate carcinoma cells, CAS, matched benign epithelium and benign epithelium-associated stroma by whole genome copy number analyses, targeted sequencing of TP53, and fluorescence in situ hybridization. Comparative genomic hybridization (aCGH) of CAS revealed a copy-neutral diploid genome with only rare and small somatic copy number aberrations (SCNAs). In contrast, several expected recurrent SCNAs were evident in the adjacent prostate carcinoma cells, including gains at 3q, 7p, and 8q, and losses at 8p and 10q. No somatic TP53 mutations were observed in CAS. Mitochondrial DNA (mtDNA) extracted from carcinoma cells and stroma identified 23 somatic mtDNA mutations in neoplastic epithelial cells but only one mutation in stroma. Finally, genomic analyses identified no SCNAs, no loss of heterozygosity (LOH) or copy-neutral LOH in cultured cancer-associated fibroblasts (CAFs), which are known to promote prostate cancer progression in vivo. Agilent whole human genome aCGH oligonucleotide microarrays were used to assess copy number aberrations in 79 specimens from 20 patients as well as two pairs of cancer-associated fibroblasts (CAF) and benign/normal associated fibroblasts (NAF). 3 CAF/NAF sample pairs were also assessed for DNA copy number aberrations and copy-neutral LOH using the Infinium HumanOmniExpressExome BeadChip Kit.
2016-02-12 | E-GEOD-76456 | biostudies-arrayexpress
Project description:Prostate cancer-associated stroma (CAS) plays an active role in malignant transformation, tumor progression, and metastasis. Molecular analyses of CAS have demonstrated significant changes in gene expression; however, conflicting evidence exists on whether genomic alterations in benign cells comprising the tumor microenvironment (TME) underlie gene expression changes and oncogenic phenotypes. This study evaluates the nuclear and mitochondrial DNA integrity of prostate carcinoma cells, CAS, matched benign epithelium and benign epithelium-associated stroma by whole genome copy number analyses, targeted sequencing of TP53, and fluorescence in situ hybridization. Comparative genomic hybridization (aCGH) of CAS revealed a copy-neutral diploid genome with only rare and small somatic copy number aberrations (SCNAs). In contrast, several expected recurrent SCNAs were evident in the adjacent prostate carcinoma cells, including gains at 3q, 7p, and 8q, and losses at 8p and 10q. No somatic TP53 mutations were observed in CAS. Mitochondrial DNA (mtDNA) extracted from carcinoma cells and stroma identified 23 somatic mtDNA mutations in neoplastic epithelial cells but only one mutation in stroma. Finally, genomic analyses identified no SCNAs, no loss of heterozygosity (LOH) or copy-neutral LOH in cultured cancer-associated fibroblasts (CAFs), which are known to promote prostate cancer progression in vivo.
2016-02-12 | GSE76456 | GEO
Project description:We used RNA-seq to interrogate prostate cancer specific gene fusions, alternative splicings, somatic mutations and novel transcripts. We sequenced the transcriptome (polyA+) of 20 prostate cancer tumors and 10 matched normal tissues using Illumina GAII platform. Then we used bioinformatic approaches to identify prostate cancer specific aberrations which include gene fusion, alternative splicing, somatic mutation, etc.
2011-05-02 | E-GEOD-22260 | biostudies-arrayexpress
Project description:Prostate tumours are highly variable in their response to therapies, but clinically available prognostic factors can explain only a fraction of this heterogeneity. Here we analysed 200 whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles, and carried out RNA and methylation analyses in a subset. These tumours had a paucity of clinically actionable single nucleotide variants, unlike those seen in metastatic disease. Rather, a significant proportion of tumours harboured recurrent non-coding aberrations, large-scale genomic rearrangements, and alterations in which an inversion repressed transcription within its boundaries. Local hypermutation events were frequent, and correlated with specific genomic profiles. Numerous molecular aberrations were prognostic for disease recurrence, including several DNA methylation events, and a signature comprised of these aberrations outperformed well-described prognostic biomarkers. We suggest that intensified treatment of genomically aggressive localized prostate cancer may improve cure rates.
2017-01-10 | GSE84042 | GEO
Project description:Prostate tumours are highly variable in their response to therapies, but clinically available prognostic factors can explain only a fraction of this heterogeneity. Here we analysed 200 whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles, and carried out RNA and methylation analyses in a subset. These tumours had a paucity of clinically actionable single nucleotide variants, unlike those seen in metastatic disease. Rather, a significant proportion of tumours harboured recurrent non-coding aberrations, large-scale genomic rearrangements, and alterations in which an inversion repressed transcription within its boundaries. Local hypermutation events were frequent, and correlated with specific genomic profiles. Numerous molecular aberrations were prognostic for disease recurrence, including several DNA methylation events, and a signature comprised of these aberrations outperformed well-described prognostic biomarkers. We suggest that intensified treatment of genomically aggressive localized prostate cancer may improve cure rates.
2017-01-10 | GSE83917 | GEO
Project description:The reason why prostate cancer is significantly more common in Western than Asian men is unknown. Using a genome-wide approach to compare the genomic changes in prostate cancer tissues, we determined that those from Chinese patients lack key somatic genomic changes commonly found in Western patients, including the 21q22.2-22.3 deletion which causes the TMPRSS2:ERG fusion gene, and 10q deletion which leads to PTEN inactivation. The results were confirmed and their consequence on ERG expression was identified by study of a large series of Chinese and UK samples using tissue-microarrays. Subsequently, we identified significant AR genotype differences between UK and Chinese prostate cancer patients. The identification of specific somatic genomic differences in cancers from distinct populations may provide an opportunity to identify cancer-causing or protective factors.
2010-05-15 | GSE18333 | GEO
Project description:Localized prostate cancer exhibits profound genomic, pathologic, and clinical heterogeneity, and current clinical prognostic factors do not accurately distinguish aggressive from indolent disease for an individual man. We and others have demonstrated that aberrant DNA methylation may be an important driver of aggressive disease. Herein, we analyze the tumor methylomes of 619 localized prostate cancers and assess the interactions between methylation and somatic tumor genomic profiles. We identify three distinct methylation subtypes, including a hypermethylation subtype which is associated with early biochemical recurrence. DNA methylation and gene copy number status synergistically regulate mRNA abundance, and aberrant methylation is strongly associated with common prostate cancer driver aberrations, including mutation density, and with altered RNA abundance profiles. Finally, we identify a set of multivariate methylation biomarkers that are prognostic of rapid biochemical recurrence. Taken together, our data provide the first comprehensive assessment of the interplay between somatic molecular phenotypes and aberrant DNA methylation in localized, non-indolent prostate cancer, and suggest that integrated genome-epigenome analyses may accurately identify men at risk for adverse clinical outcomes in this patient cohort.
2019-06-30 | GSE107298 | GEO
Project description:DNA sequencing studies have identified specific recurrent somatic mutations that drive the aggressiveness of localized prostate cancers. Surprisingly, though, it is poorly understood how the prostate cancer proteome is shaped by genomic, epigenomic and transcriptomic dysregulation. To fill this gap, we profiled the whole genomes, methylomes, epigenomes, transcriptomes and proteomes of 55 localized, intermediate-risk, prostate cancers. This multi-modal dataset revealed that the genomic subtypes of prostate cancer converge on four proteomic subtypes, which are associated with distinct clinical trajectories. ETS fusion genes, the most common mutation in prostate tumours, perturb the proteome and transcriptome in divergent ways – with different genes and pathways affected at each level. Indeed, mRNA abundance changes explain only ~10% of variability in protein levels. Perhaps as a direct result, prognostic biomarkers that combine genomic or epigenomic features with proteomic ones significantly outperform those comprised of either molecular feature alone. These data suggest that the proteome of prostate cancer is shaped by a complex interplay of genomic, epigenomic, transcriptomic and post-transcriptional dysregulation.
2019-06-30 | GSE107299 | GEO
Project description:We used DNA content-based flow cytometry to distinguish and isolate nuclei from clonal populations in primary tissues from three disparate cancers with variable clinical histories. We then developed a methodology to adapt flow cytometrically purified nuclei samples for use with whole genome technologies including aCGH and next generation sequencing (NGS). Our results demonstrate that selected aberrations in the genomes of distinct clonal populations in each patient create clinically relevant contexts at least with respect to the cancer types profiled in this study. We applied DNA content based flow sorting to isolate the nuclei of clonal populations from tumor biopsies. Genomic DNA from each sorted population was amplified with phi29 polymerase. A 1ug aliquot of each amplified sample was digested with DNAse 1 then labeled with Cy5 using a Klenow-based commercial kit (Invitrogen). Each sample was hybridized with a pooled normal (46,XX) reference (Promega) to Agilent 244k CGH arrays. The use of highly purified objectively defined flow sorted populations provides high definition genomic profiles of clonal populations from pancreatic adenocarcinomas (PA), adrenal cortical carcinomas (ACC), and prostate adenocarcinomas (PC).
2011-07-04 | E-GEOD-21660 | biostudies-arrayexpress
Project description:Many human cancers present as multi-focal lesions. Understanding the clonal origin of multi-focal cancers is of both etiological and clinical importance. The molecular basis of multi-focal prostate cancer has previously been explored using only a limited number of isolated markers and, although independent origin is widely believed, the clonal origin of multi-focal prostate cancer is still debatable. We attempted to address clonal origin using a genome-wide copy-number analysis of individual cancer and high-grade prostatic intraepithelial neoplasia (HGPIN) lesions. Using Affymetrix array 6.0 copy-number analysis, we compared the genomic changes detected in 54 individual cancer and HGPIN lesions, isolated from 20 clinically localized prostate cancer cases. Identical genomic copy-number changes, shared by all same-case cancer foci, were detected in all 16 informative multi-tumor cases. In addition, both HGPIN lesions in the two multi-HGPIN cases available shared identical genomic changes. Commonly known genomic alterations, including losses at 6q15, 8p21.3-8p21.2, 10q23.2-10q23.31, 13q21.31-13q21.32, 16q22.3, 16q23.2-16q23.3 and 21q22.2-21q22.3 regions and gain of 8q24.3 were the most frequently detected changes in this multi-focal prostate cancer study, occurring in all same-case foci in at least one case. Microarray data were confirmed by fluorescence in situ hybridization in selected foci. Our high-resolution genome-wide copy-number data suggest that many multi-focal cases derive from a single prostate cancer precursor clone and that this precursor may give rise to separate HGPIN foci, which through clonal expansion may progress to multi-focal invasive prostate cancer. These findings, which demonstrate the monoclonal origin of multi-focal prostate cancer, should significantly enhance our understanding of prostate carcinogenesis and potentially improve clinical management of the disease. Copy number analysis of Affymetrix SNP 6.0 array was performed for a total of 48 cancer and HGPIN lesions from 18 prostate cancer cases. All samples have case-matched normal controls. PL = high grade PIN from left side, PR = high grade PIN from right side, PM = high grade PIN from middle of the tissue, TL = tumour from left side, TR = tumour from right side.
2011-12-31 | E-GEOD-29569 | biostudies-arrayexpress