Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA327864 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Genomic hallmarks of localized, non-indolent prostate cancer
| PRJNA327408 | ENA
Project description:Genomic hallmarks of localized, non-indolent prostate cancer
| PRJNA327861 | ENA
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: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: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:Epigenomic alterations in localized and advanced prostate cancer
| PRJNA177992 | ENA
Project description:A major challenge in the clinical management of prostate cancer is the inability to definitively diagnose indolent versus aggressive cases. Contributing to this challenge is a lack of basic science understanding of the molecular basis behind aggressiveness subtypes in prostate cancer. DNA methylation is the epigenetic addition of a methyl group to the DNA base cytosine and has been found to regulate cell proliferation and environmental adaptation. We hypothesized that DNA methylation changes are a mechanism by which an aggressive cancer attains phenotypes that distinguish it from indolent cases via disruption of regulatory networks. This hypothesis was tested by comparing DNA methylation between benign prostate and both low grade (Gleason score 6) and high grade (Gleason score 8 to 10) groups. Methylome-wide next generation sequencing was performed on formalin-fixed paraffin embedded (FFPE) samples from radical prostatectomy cases using MBD-isolated genome sequencing (MiGS). This technique uses a DNA methylation binding protein (MBD) to purify fragments from a genomic library with a high level of CpG DNA methylation. These fragments were then sequenced via next generation sequencing, the reads were aligned to a reference genome, and then the reads were counted within non-overlapping 50bp windows genome wide. Statistical analysis was then performed on these windowed counts to produce differentially methylated regions (DMRs). MBD-isolated Genome Sequencing (MiGS) for groups of benign prostate (from cystoprostatectomy), low grade prostate cancer (from radical prostatectomy with Gleason Score 6), and high grade prostate cancer (from radical prostatectomy with Gleason Scores 8 to 10) in both European Americans and African Americans
2015-11-01 | E-GEOD-66505 | biostudies-arrayexpress
Project description:Expression data for primary localized prostate cancer versus castration-resistant bone metastatic prostate cancer
| PRJNA147325 | ENA
Project description:Clinical management of prostate cancer remains a significant challenge due to the lack of available tests for guiding treatment decisions. The blood Prostate-Specific Antigen (PSA) test has facilitated early detection and intervention of prostate cancer. However, blood PSA levels are less effective in distinguishing aggressive from indolent prostate cancers and other benign prostatic diseases. Thus, the development of novel approaches specific for prostate cancer that can differentiate aggressive from indolent disease remains an urgent medical need. In the current study, we evaluated urine specimens from prostate cancer patients instead of serum using liquid chromatography-tandem mass spectrometry (LC-MS/MS), with the aim of identifying effective prostate cancer biomarkers. Glycoproteins from urine samples of prostate cancer patients with different Gleason scores were characterized via solid phase extraction of N-linked glycosite-containing peptides and LC-MS/MS. In total, 2923 unique glycosite-containing peptides were identified. Comparison of urine-based glycoproteins with those identified from aggressive and non-aggressive prostate cancer tissues as well as sera from prostate cancer patients revealed that the majority of aggressive prostate cancer-associated glycoproteins were more readily detected in patient urine than serum samples. Our data collectively indicate that urine provides a highly reliable source for biomarker testing in patients with aggressive prostate cancer.
2022-02-28 | PXD004495 | Pride
Project description:Prostate cancer is the Prostate cancer is the most prevalent cancer in men. However, the majority of prostate cancers diagnosed today are indolent with 14% of patients diagnosed with lethal prostate cancer. It is of great importance to determine the molecular features that are involved in the aggressiveness of prostate cancers. To this end, we found that through SWATH-MS proteomics analyses of 108 well-preserved frozen prostate tissues of various disease states, tmost prevalent cancer in men. However, the majority of prostate cancers diagnosed today are indolent with 14% of patients diagnosed with lethal prostate cancer. It is of great importance to determine the molecular features that are involved in the aggressiveness of prostate cancers. To this end, we deployed SWATH-MS proteomics analyses of 108 well-preserved frozen prostate tissues of various disease states.
2022-02-28 | PXD002306 | Pride