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Genomic "Dark Matter" in Prostate Cancer: Exploring the Clinical Utility of ncRNA as Biomarkers.

Ismael A Vergara | Nicholas Erho | Timothy J Triche | Mercedeh Ghadessi | Anamaria Crisan | Thomas Sierocinski | Peter C Black | Christine Buerki | Elai Davicioni
Frontiers in genetics | 2012

Prostate cancer is the most diagnosed cancer among men in the United States. While the majority of patients who undergo surgery (prostatectomy) will essentially be cured, about 30-40% men remain at risk for disease progression and recurrence. Currently, patients are deemed at risk by evaluation of clinical factors, but these do not resolve whether adjuvant therapy will significantly attenuate or delay disease progression for a patient at risk. Numerous efforts using mRNA-based biomarkers have been described for this purpose, but none have successfully reached widespread clinical practice in helping to make an adjuvant therapy decision. Here, we assess the utility of non-coding RNAs as biomarkers for prostate cancer recurrence based on high-resolution oligonucleotide microarray analysis of surgical tissue specimens from normal adjacent prostate, primary tumors, and metastases. We identify differentially expressed non-coding RNAs that distinguish between the different prostate tissue types and show that these non-coding RNAs can predict clinical outcomes in primary tumors. Together, these results suggest that non-coding RNAs are emerging from the "dark matter" of the genome as a new source of biomarkers for characterizing disease recurrence and progression. While this study shows that non-coding RNA biomarkers can be highly informative, future studies will be needed to further characterize the specific roles of these non-coding RNA biomarkers in the development of aggressive disease.

Pubmed ID: 22371711

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Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


Ensembl (tool)

RRID:SCR_002344

Collection of genome databases for vertebrates and other eukaryotic species with DNA and protein sequence search capabilities. Used to automatically annotate genome, integrate this annotation with other available biological data and make data publicly available via web. Ensembl tools include BLAST, BLAT, BioMart and the Variant Effect Predictor (VEP) for all supported species.

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ExPANdS (tool)

RRID:SCR_005199

Software that characterizes coexisting subpopulations (SPs) in a tumor using copy number and allele frequencies derived from exome- or whole genome sequencing input data. The model amplifies the statistical power to detect coexisting genotypes, by fully exploiting run-specific tradeoffs between depth of coverage and breadth of coverage. ExPANdS predicts the number of clonal expansions, the size of the resulting SPs in the tumor bulk, the mutations specific to each SP and tumor purity. The main function runExPANdS provides the complete functionality needed to predict coexisting SPs from single nucleotide variations (SNVs) and associated copy numbers. The robustness of the subpopulation predictions by ExPANdS increases with the number of mutations provided. It is recommended that at least 200 mutations are used as an input to obtain stable results.

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X:MAP (tool)

RRID:SCR_006029

X:Map is a project for mapping between Affymetrix Exon Arrays and their corresponding genome data. It consists of a website for general visualisation of Gene/Transcript/Exon/Probeset relationships, and an R package exonmap to support statistical analysis of Exon Array experiments. Affymetrix exon arrays aim to target every known and predicted exon in the human, mouse or rat genomes, and have reporters that extend beyond protein coding regions to other areas of the transcribed genome. This combination of increased coverage and precision is important because a substantial proportion of protein coding genes are predicted to be alternatively spliced, and because many non-coding genes are known also to be of biological significance. In order to fully exploit these arrays, it is necessary to associate each reporter on the array with the features of the genome it is targeting, and to relate these to gene and genome structure. X:Map is a genome annotation database that provides this information. Data can be browsed using a novel Google-maps based interface, and analysed and further visualized through an associated BioConductor package.

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Bioconductor (tool)

RRID:SCR_006442

Software repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.

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NCBI (tool)

RRID:SCR_006472

A portal to biomedical and genomic information. NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease.

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Affymetrix (tool)

RRID:SCR_007817

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 17,2023. Affymetrix is a partially commercial resource that provides DNA Analysis Arrays, Expression Analysis Arrays, Gene Regulation Analysis, and Microarrays. It also provides reagents and assays, instruments, software, and services for a fee. Information is provided for Rats, Humans, and Mice.Affymetrix is now Applied Biosystems, brand of DNA microarray products sold by Thermo Fisher Scientific that originated with an American biotechnology research and development and manufacturing company of the same name.

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vegan (tool)

RRID:SCR_011950

Ordination methods, diversity analysis and other functions for community and vegetation ecologists.

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fRMA (tool)

RRID:SCR_001345

Preprocessing and analysis software for single microarrays and microarray batches.

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